Prospective, randomized, double-blind, placebo-controlled evaluation of the Pharmacokinetics, Safety and Efficacy of Recombinant Antithrombin Versus Placebo in Preterm Preeclampsia.

BACKGROUND: Despite expectant management, preeclampsia remote from term usually results in preterm delivery. Antithrombin, which displays antiinflammatory and anticoagulant properties, may have a therapeutic role in treating preterm preeclampsia, a disorder characterized by endothelial dysfunction, inflammation, and activation of the coagulation system. OBJECTIVE: This randomized, placebo-controlled clinical trial aimed to evaluate whether intravenous recombinant human antithrombin could prolong gestation and therefore improve maternal and fetal outcomes. STUDY DESIGN: We performed a double-blind, placebo-controlled trial at 23 hospitals. Women were eligible if they had a singleton pregnancy, early-onset or superimposed preeclampsia at 23 0/7 to 30 0/7 weeks' gestation, and planned expectant management. In addition to standard therapy, patients were randomized to receive either recombinant human antithrombin 250 mg loading dose followed by a continuous infusion of 2000 mg per 24 hours or an identical saline infusion until delivery. The primary outcome was days gained from randomization until delivery. The secondary outcome was composite neonatal morbidity score. A total of 120 women were randomized. RESULTS: There was no difference in median gestational age at enrollment (27.3 weeks' gestation for the recombinant human antithrombin group [range, 23.1-30.0] and 27.6 weeks' gestation for the placebo group [range, 23.0-30.0]; P=.67). There were no differences in median increase in days gained (5.0 in the recombinant human antithrombin group [range, 0-75] and 6.0 for the placebo group [range, 0-85]; P=.95). There were no differences between groups in composite neonatal morbidity scores or in maternal complications. No safety issues related to recombinant human antithrombin were noted in this study, despite the achievement of supraphysiological antithrombin concentrations. CONCLUSION: The administration of recombinant human antithrombin in preterm preeclampsia neither prolonged pregnancy nor improved neonatal or maternal outcomes.

Effects of Maternal Carbohydrate and Fat Intake on Fetal Telomere Length.

OBJECTIVES: Telomere length can be affected by dietary factors in adults. We investigated the association between maternal carbohydrate and fat intake during pregnancy and telomere length in neonatal cord blood leukocytes. We hypothesized that high fat consumption and high carbohydrate consumption would be associated with shortened fetal telomere length. METHODS: We collected umbilical cord blood at delivery from women admitted for labor and delivery in a university hospital (N = 62) and extracted genomic DNA using quantitative polymerase chain reaction. We quantified telomere length using the telomere-to-single copy gene ratio method (T:S ratio). High carbohydrate intake was defined as consumption of >175 g/day and high fat intake as >35 g/day. We performed generalized linear regression modeling and bootstrap statistical analyses to derive precise estimates of association. RESULTS: Of the 62 maternal-fetal dyads included in this study, 79% were classified as high carbohydrate consumers and 37% were classified as high fat consumers. High fat consumption had a significant negative effect on T:S ratio (P < 0.05). Although high carbohydrate consumption was associated with a decreased T:S ratio, this relation did not attain statistical significance. CONCLUSIONS: To our knowledge, this study is the first evidence of an association between maternal high fat consumption and shortened fetal telomere length. These findings could enhance our understanding of the role of maternal diet in fetal programming.

Telomere length and fetal programming: A review of recent scientific advances.

We sought to synthesize a comprehensive literature review comprising recent research linking fetal programming to fetal telomere length. We also explored the potential effects fetal telomere length shortening has on fetal phenotypes. Utilizing the PubMed database as our primary search engine, we retrieved and reviewed 165 articles of published research. The inclusion criteria limited the articles to those that appeared within the last ten years, were pertinent to humans, and without restriction to language of publication. Our results showed that socio-demographic factors like age, sex, genetic inheritance, and acquired disease impact telomere length. Further, we found several maternal characteristics to be associated with fetal telomere length shortening, and these include maternal chemical exposure (eg, tobacco smoke), maternal stress during pregnancy, maternal nutritional and sleeping disorders during pregnancy as well as maternal disease status. Due to paucity of data, our review could not synthesize evidence directly linking fetal phenotypes to telomere length shortening. Although the research summarized in this review shows some association between determinants of intrauterine programming and fetal telomere length, there is still significant work that needs to be done to delineate the direct relationship of telomere attrition with specific fetal phenotypes.

Evidence of altered brain regulatory gene expression in tobacco-exposed fetuses.

AIM: We sought to determine the association between prenatal smoking status and expression of fetal brain regulatory genes. METHODS: At delivery, we collected information from parturient women on prenatal smoking habits and analyzed salivary cotinine levels. We obtained neonatal umbilical cord blood and extracted total RNA. We then employed the quantitative polymerase chain reaction (QPCR) analyses and the comparative CT method to calculate the relative gene expression of selected fetal brain regulatory genes responsible for (1) brain growth (brain-derived neutrotrophic factor, BDNF), (2) myelination (proteolipidic protein 1, PLP1 and myelin basic protein, MBP), and (3) neuronal migration and cell-cell interactions during fetal brain development or RLN. The χ2-test, analysis of variance (ANOVA), and the Grubb test were used to evaluate the relationship between prenatal smoking status and relative gene expression levels. Further analysis using bootstrapping was performed to assess the precision of our estimates. RESULTS: Of the 39 maternal-infant dyads included in this study, 25.6% were non-smokers, 43.6% were passive smokers and 30.8% were active smokers. The results showed down-regulation of the selected fetal brain regulatory genes among active smokers. CONCLUSIONS: These findings represent preliminary evidence in humans that intrauterine tobacco exposure impacts fetal brain programming. Future studies are warranted to examine whether our findings represent potential mechanisms through which adverse childhood/adult-onset cognitive and behavioral outcomes that have been previously linked to intrauterine exposure occur.

Association Between Maternal-Perceived Psychological Stress and Fetal Telomere Length.

OBJECTIVE: Our study aimed to investigate the association between maternal-perceived psychological stress and fetal telomere length. METHODS: We recruited women in labor upon hospital delivery admission. Based on responses to the Perceived Stress Scale, we categorized participants as having "high," "normal," or "low" perceived stress. We collected umbilical cord blood samples (N = 71) and isolated genomic DNA from cord blood leukocytes using quantitative polymerase chain reaction. We used a ratio of relative telomere length derived by telomere-to-single-copy gene ratio (T/S ratio). We applied analysis of variance and bootstrapping statistical procedures. RESULTS: Sixteen (22.5%) women were classified as having low perceived stress, 42 (59.2%) were classified as having normal perceived stress, and 13 (18.3%) were classified as having high perceived stress. Fetal telomere length differed significantly across the three stress groups in a dose-response pattern (T/S ratio of those with low perceived stress was greater than those with normal perceived stress, which was greater than those with high perceived stress [P < 0.05]). CONCLUSIONS: Our findings support our hypothesis that maternal-perceived psychological stress during pregnancy is associated with shorter fetal telomere length and suggest maternal stress as a possible marker for early intrauterine programming for accelerated chromosomal aging.

A positive association between umbilical cord RBC folate and fetal TL at birth supports a potential for fetal reprogramming.

Telomere length (TL) has been studied extensively in adults; however, limited information exists regarding maternal influences on TL in utero. The objective of this study was to investigate the relationship between fetal red blood cell (RBC) folate levels, a surrogate measure for maternal folate levels, and TL. We hypothesized that umbilical cord RBC folate concentrations would positively correlate with fetal TL. Data for this analysis were collected as part of a prospective cohort study that recruited pregnant women upon admission into labor and delivery. Cord blood was collected for 96 maternal-fetal dyads, and DNA analysis was performed using quantitative polymerase chain reaction. The telomere to single copy gene ratio method was used to determine TL, and RBC folate levels were measured. Statistical analysis was conducted by incorporating a bootstrapping approach into generalized linear modeling-based analyses. Consistent significant positive correlations were observed between RBC folate and TL (telomere to single copy gene ratio) with 9880 of the 10000 (98.8%) iterations performed having a P value less than .05. Our study shows a positive association between umbilical cord RBC folate and fetal TL at birth. These findings may provide a pathway of understanding and preventing adult-onset disease and mortality through intrauterine reprogramming.

Homocysteine Levels Are not Related to Telomere Length in Cord Blood Leukocytes of Newborns.

Objective Elevated homocysteine (HC) levels and/or shortened telomere length (TL) are associated with adverse medical conditions. Our objective is to investigate the relationship between HC and TL in cord blood leukocytes of newborns. Study Design This is a nested study from a prospective cohort from 2011 to 2012 in pregnant women admitted for delivery at a university-affiliated hospital. Cord blood was collected at delivery and genomic DNA was analyzed using quantitative PCR. The telomere-to-single copy gene ratio method was employed to quantify TL. Newborn HC levels were measured. generalized linear regression modeling (GLM) and bootstrap statistical analyses were performed. Results Seventy-seven maternal-fetal dyads with a mean gestational age of 39 weeks were included. The distribution of the coefficient of homocysteine showed most values greater than zero demonstrating that homocysteine had a positive relationship with TL. In 915 of 10,000 (9.15%) iterations, the p-value was < 0.05 demonstrating a positive effect. Conclusion Increasing newborn concentrations of HC are not associated with decreasing TL. Larger, prospective studies are needed to confirm these findings and long-term implications.

Recent trends in placenta accreta in the United States and its impact on maternal-fetal morbidity and healthcare-associated costs, 1998-2011.

OBJECTIVE: To describe the prevalence, trends, adverse maternal-fetal morbidities and healthcare costs associated with placenta accreta (PA) in the United States (US) between 1998 and 2011. METHODS: A retrospective, cross-sectional analysis of inpatient hospital discharges was conducted using the National Inpatient Sample (NIS). We used International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) codes to identify both cases of PA and of selected comorbidities. Survey logistic regression was used to assess the association between PA and various maternal-fetal outcomes. Joinpoint regression modeling was used to estimate annual percent changes (APCs) in PA prevalence during the study period. RESULTS: The prevalence of PA from 1998 to 2011 was 3.7 per 1000 delivery-related discharges. After adjusting for known or suspected confounders, PA conferred between a 20% to over a 19-fold increased odds of experiencing an adverse outcome. This resulted in a higher mean, per-hospitalization, cost of inpatient care after adjustment for inflation ($5561 versus $4989), translating into over $115 million dollars in additional inpatient expenditures relative to non-PA affected deliveries from 2001 to 2011. CONCLUSIONS: This study updates recent trends in the prevalence of PA, which is valuable to clinicians and policymakers as they formulate targeted strategies to address factors related to PA.

Additive effects of Pre-pregnancy body mass index and gestational diabetes on health outcomes and costs.

OBJECTIVE: Pre-pregnancy obesity and gestational diabetes mellitus (GDM) are increasingly prevalent independent risk factors for maternal and infant morbidities. However, there is a paucity of information on their joint effects on health outcomes and healthcare costs. METHODS: A population-based retrospective cohort study was conducted in Florida using a validated statewide database covering 1,057,647 infants born between 2004 and 2009. Using generalized linear modeling, joint associations between levels of pre-pregnancy body mass index (BMI) and GDM and maternal complications of pregnancy, adverse birth outcomes, and healthcare costs were examined. The relative excess risk due to interaction was used to describe the direction and magnitude of the BMI-GDM interaction on the additive scale. RESULTS: Increasing pre-pregnancy BMI conferred increasing odds of adverse consequences, as did GDM, and the BMI-GDM interaction was greater than additive for 9 of 14 outcomes. The cost for infants born to women with GDM/obesity-III was 34% higher during the first year compared with those born to women with normal BMI and without GDM. The costs of maternal and infant inpatient care associated with overweight/obesity and GDM totaled over $351 million. CONCLUSIONS: These findings provide further evidence of the importance of lifestyle modifications to decrease rates of obesity and risk factors from GDM.

National trends in maternal use of opioid drugs among pregnancy-related hospitalizations in the United States, 1998 to 2009.

OBJECTIVE: The aim of this study is to describe national trends for opioid use among pregnancy-related hospitalizations from 1998 to 2009. STUDY DESIGN: Using the Nationwide Inpatient Sample, we identified hospital discharge records associated with the diagnoses codes for the use of opioids for all eligible pregnancy-related inpatient admissions between 1998 and 2009. Joinpoint regression modeling was used to describe changes in trend of pregnancy-related opioid use. The main outcome measure was the annual percent change for opioids use among pregnancy-related hospitalizations. RESULTS: From 1998 to 2009, opioid use was documented in 138,224 of 55,781,966 pregnancy-related inpatient hospitalizations (25 cases per 10,000 discharges). A statistically significant downward trend occurred from 1998 to 2001, whereas from 2002 to 2009 there was a statistically significant upward trend. The increasing trend in opioid use from 2002 to 2009 is notably higher for whites compared with blacks and Hispanics. CONCLUSIONS: Our findings highlight the continuous need to monitor opioids use and to revise prescription guidelines, practices, and regulatory mechanisms to curtail the progression of the increasing opioids use during pregnancy. It is critical that health care providers weight the benefits of these medications along with their potential risks when discussing analgesic treatment options with pregnant women.

Impact of intrauterine tobacco exposure on fetal telomere length.

OBJECTIVE: We sought to investigate whether maternal smoking during pregnancy affects telomere length of the fetus. STUDY DESIGN: Pregnant women were recruited on hospital admission at delivery. A self-report questionnaire and salivary cotinine test were used to confirm tobacco exposure. Neonatal umbilical cord blood samples were collected, and genomic DNA was isolated from cord blood leukocytes and was analyzed for fetal telomere length based on quantitative polymerase chain reaction. A ratio of relative telomere length was determined by telomere repeat copy number and single copy gene copy number (T/S ratio) and used to compare the telomere length of active, passive, and nonsmokers. Bootstrap and analysis of variance statistical methods were used to evaluate the relationship between prenatal smoking status and fetal telomere length. RESULTS: Of the 86 women who were included in this study, approximately 69.8% of the participants were covered by Medicaid, and 55.8% of the participants were black or Hispanic. The overall mean T/S ratio was 0.8608 ± 1.0442. We noted an inverse relationship between smoking and fetal telomere length in a dose-response pattern (T/S ratio of nonsmokers that was more than passive smokers that was more than active smokers). Telomere length was significantly different for each pairwise comparison, and the greatest difference was between active and nonsmokers. CONCLUSION: Our results provide the first evidence to demonstrate a positive association between shortened fetal telomere length and smoking during pregnancy. Our findings suggest the possibility of early intrauterine programming for accelerated aging that is the result of tobacco exposure.

Association between maternal symptoms of sleep disordered breathing and fetal telomere length.

STUDY OBJECTIVES: Our investigation aims to assess the impact of symptoms of maternal sleep-disordered breathing, specifically sleep apnea risk and daytime sleepiness, on fetal leukocyte telomere length. PARTICIPANTS AND SETTING: Pregnant women were recruited upon hospital delivery admission. INTERVENTIONS: Sleep exposure outcomes were measured using the Berlin Questionnaire to quantify sleep apnea and the Epworth Sleepiness Scale to measure daytime sleepiness. Participants were classified as "High Risk" or "Low Risk" for sleep apnea based on responses to the Berlin, while "Normal" or "Abnormal" daytime sleepiness was determined based on responses to the Epworth. DESIGN: Neonatal umbilical cord blood samples (N = 67) were collected and genomic DNA was isolated from cord blood leukocytes using Quantitative PCR. A ratio of relative telomere length was derived by telomere repeat copy number and single copy gene copy number (T/S ratio) and used to compare telomere lengths. Bootstrap and ANOVA statistical procedures were employed. MEASUREMENTS AND RESULTS: On the Berlin, 68.7% of participants were classified as Low Risk while 31.3% were classified as High Risk for sleep apnea. According to the Epworth scale, 80.6% were determined to have Normal daytime sleepiness, and 19.4% were found to have Abnormal daytime sleepiness. The T/S ratio among pregnant women at High Risk for sleep apnea was significantly shorter than for those at Low Risk (P value < 0.05), and the T/S ratio among habitual snorers was significantly shorter than among non-habitual snorers (P value < 0.05). Although those with Normal Sleepiness had a longer T/S ratio than those with Abnormal Sleepiness, the difference was not statistically significant. CONCLUSION: Our results provide the first evidence demonstrating shortened telomere length among fetuses exposed to maternal symptoms of sleep disordered breathing during pregnancy, and suggest sleep disordered breathing as a possible mechanism of accelerated chromosomal aging.

Socio-ecological Model as a Framework for Overcoming Barriers and Challenges in Randomized Control Trials in Minority and Underserved Communities.

BACKGROUND: Numerous barriers and challenges can hinder the successful enrollment and retention of study participants in clinical trials targeting minority populations. To conduct quality research, it is important to investigate these challenges, determine appropriate strategies that are evidence-based and continue seeking methods of improvement. METHODS: In this paper, we report such experiences in a registered clinical trial in an underserved minority population in the Southern part of United States. This research study is a randomized double-blind controlled clinical trial that tests the efficacy of higher-strength as compared to low-strength/standard of care folic acid to prevent fetal body and brain size reduction in pregnant women who smoke. A unique approach in this socio-behavioral, genetic-epigenetic clinical trial is that we have adopted the socio-ecological model as a functional platform to effectively achieve and maintain high participant recruitment and retention rates. RESULTS: We highlight the barriers we have encountered in our trial and describe how we have successfully applied the socio-ecological model to overcome these obstacles. CONCLUSIONS AND GLOBAL HEALTH IMPLICATIONS: Our positive experience will be of utility to other researchers globally. Our fi ndings have far-reaching implications as the socio-ecological model approach is adaptable to developed and developing regions and has the potential to increase recruitment and retention of hard-to-reach populations who are typically under-represented in clinical trials.

Maternal opioid drug use during pregnancy and its impact on perinatal morbidity, mortality, and the costs of medical care in the United States.

OBJECTIVE: To identify factors associated with opioid use during pregnancy and to compare perinatal morbidity, mortality, and healthcare costs between opioid users and nonusers. METHODS: We conducted a cross-sectional analysis of pregnancy-related discharges from 1998 to 2009 using the largest publicly available all-payer inpatient database in the United States. We scanned ICD-9-CM codes for opioid use and perinatal outcomes. Costs of care were estimated from hospital charges. Survey logistic regression was used to assess the association between maternal opioid use and each outcome; generalized linear modeling was used to compare hospitalization costs by opioid use status. RESULTS: Women who used opioids during pregnancy experienced higher rates of depression, anxiety, and chronic medical conditions. After adjusting for confounders, opioid use was associated with increased odds of threatened preterm labor, early onset delivery, poor fetal growth, and stillbirth. Users were four times as likely to have a prolonged hospital stay and were almost four times more likely to die before discharge. The mean per-hospitalization cost of a woman who used opioids during pregnancy was $5,616 (95% CI: $5,166-$6,067), compared to $4,084 (95% CI: $4,002-$4,166) for nonusers. CONCLUSION: Opioid use during pregnancy is associated with adverse perinatal outcomes and increased healthcare costs.

Perinatal outcomes and hospital costs in gastroschisis based on gestational age at delivery.

OBJECTIVE: To investigate the association between gestational age at delivery and perinatal outcomes among gastroschisis-affected pregnancies that result in live birth. METHODS: We conducted a retrospective cohort study using a linked maternal-infant database for more than 2.3 million liveborn neonates in Florida from 1998 to 2009. Cases were identified using a combination of International Classification of Diseases, 9th Edition, Clinical Modification, diagnosis and procedure codes indicative of gastroschisis. We restricted our analyses to singleton cases without another major birth defect or medical conditions that would justify early elective delivery. We categorized cases based on gestational age in weeks and compared perinatal outcomes. RESULTS: Among 1,005 neonates with gastroschisis, 324 (32.3%) were isolated, singleton cases without an additional indication for early delivery. We observed decreased rates of adverse pregnancy outcomes among those neonates delivered in the early term period (37-38 weeks of gestation) compared with preterm (less than 34 weeks of gestation); specifically, jaundice (18.5% compared with 42.3%, P=.01) and respiratory distress syndrome (5.9% compared with 23.1%, P≤.01). As the gestational age at birth increased, we observed fewer mean number of days spent in the hospital (less than 34 weeks of gestation: 55.9, P<.01; 34-36 weeks of gestation: 51.9, P=.02; 37-38 weeks of gestation: 36.9 [reference]) and lower direct inpatient medical costs (in thousands, U.S. dollars; less than 34 weeks of gestation: 79, P=.01; 34-36 weeks of gestation: 71, P=.04; 37-38 weeks of gestation: 51 [reference]) per infant in the first year of life. CONCLUSION: In pregnancies complicated by gastroschisis, and with no other known major indications, birth at early term or later term gestation, when compared with delivery before 37 weeks of gestation, is associated with improved perinatal outcomes and lower medical costs. LEVEL OF EVIDENCE: II.

Positive interferon-γ release assay leading to a diagnosis of Mycobacterium tuberculosis pericarditis in pregnancy.

BACKGROUND: Tuberculosis during pregnancy is associated with increased complications. The wide range of presentations among patients with extrapulmonary tuberculosis can make diagnosis and treatment difficult. CASE: We present the case of a patient with Mycobacterium tuberculosis pericarditis presenting in pregnancy with recurrent pericardial effusions. The diagnosis of active tuberculosis was made and treatment initiated after a positive interferon-gamma release assay and granulomatous pericardial pathology despite negative tuberculin skin testing. Culture of pericardial tissue obtained by pericardectomy confirmed the diagnosis 1 month after initiation of treatment. CONCLUSION: This case report demonstrates the use of interferon-gamma release assay in diagnosing tuberculosis among high-risk pregnant patients. Although limited by expense and minimal experience in pregnancy, these assays may be useful to screen for tuberculosis in high-risk pregnant populations.

Postmortem ultrasonography of the macerated fetus complements autopsy following in utero fetal demise.

Postmortem evaluation following an in utero fetal demise is essential for determining cause of death and counseling regarding future pregnancies. Severe maceration and fetal size along with patient desires may limit the physician's ability to perform a complete autopsy. In the cases presented, we demonstrate the utility of postmortem ultrasonography as an adjunct to traditional autopsy following fetal demise.

Impact of sickle cell disease and thalassemias in infants on birth outcomes.

OBJECTIVE: The contribution of sickle cell disease (SCD) and other common thalassemias in infants to adverse birth outcomes is under-studied. We therefore sought to compare adverse birth outcomes in infants with and without hemoglobinopathy. STUDY DESIGN: Retrospective cohort study utilizing a population-based dataset from Florida (1998-2007, n=1,564,038). The primary outcomes were low birthweight (LBW), very low birthweight (VLBW), preterm birth (PTB), very preterm birth (VPTB) and small for gestational age (SGA). We used propensity scores to match infants with hemoglobinopathy to those without hemoglobinopathy on selected variables. To approximate relative risks, we generated adjusted odds ratios (AOR) and 95% confidence intervals (CI) from logistic regression models and accounted for the matched design using generalized estimating equations framework. RESULTS: Infants with SCD or thalassemia had a heightened risk for LBW (AOR=1.58, 95% CI: 1.29-1.93), VLBW (AOR=3.01, 95% CI: 2.12-4.25), PTB (AOR=1.36, 95% CI: 1.12-1.65), VPTB (AOR=2.70, 95% CI: 1.93-3.78), and neurological conditions (AOR=2.04, 95% CI: 1.48-2.81) compared to infants without hemoglobinopathy. CONCLUSION: Infants with SCD or thalassemia experience considerably higher risks for multiple infant morbidities. Our findings are potentially important in prenatal counseling, as well as for targeted care of affected pregnancies in the prenatal period.

The maternal, fetal, and neonatal effects of cocaine exposure in pregnancy.

Despite multiple efforts to reduce the use of illicit drugs, the epidemic of addiction continues to be a significant public health issue. Through its easy availability, the number of people afflicted with this addiction continues to rise, including women of childbearing age. Secondarily, any health care crisis that occurs in this age group of women will have potential implications in pregnancy, infancy, and childhood. The use of cocaine alone or in conjunction with other illicit drugs, combined with the normal physiological cardiovascular changes in pregnancy, leads to a myriad of pathophysiological changes, thereby placing the life of the pregnant cocaine user, as well as the health status of their unborn fetus and neonate at risk for adverse outcomes. As more data are available, the long-term physical, mental, and developmental sequelae for children exposed to cocaine in utero prove that this public health crisis has serious implications. The pregnancy-specific maternal, fetal, and neonatal risks of cocaine use during the antepartum period are reviewed.

Association between reproductive cancer and fetal outcomes: a population-based study.

PURPOSE: This study aimed to evaluate the impact of maternal reproductive cancer diagnosis on fetal birth outcomes. MATERIALS AND METHODS: We conducted a retrospective population-based cohort study among women with a singleton live birth and diagnosed with reproductive cancer in the state of Florida (cases). We matched cases to cancer-free controls using selected sociodemographic and pregnancy-related clinical conditions. We applied logistic regression with correction for intracluster correlation using generalized estimating equations. RESULTS: Overall, 3212 (0.21%) of pregnant women had a diagnosis of reproductive cancer. Affected women had a 24% and 33% elevated risk for low birth weight (LBW) and preterm birth (PTB) infants, respectively. Compared to their white counterparts, black women with reproductive cancer had a greater risk for LBW [odds ratio (OR), 1.83; 95% confidence interval (CI), 1.37-2.44], small for gestational age (SGA) [OR, 1.64; 95% CI, 1.23-2.17], and PTB (OR, 1.47; 95% CI, 1.12-192) infants. Black women with breast cancer demonstrated significantly higher risks of LBW [adjusted odds ratio (AOR), 2.37; 95% CI, 1.56-3.60], PTB (AOR, 1.71; 95% CI, 1.15-2.56), and SGA (AOR, 1.72; 95% CI, 1.12-2.64) when compared to women of their racial group with no reproductive cancer. CONCLUSIONS: Diagnosis of reproductive cancer before or during pregnancy and within 30 days after birth is associated with adverse fetal outcomes (LBW, PTB, and SGA). These results highlight the importance of preconception and intraconception care of women with reproductive cancer diagnosis.