Oscar A. Viteri

Diabetic ketoacidosis in pregnancy

Pregnancies complicated by diabetic ketoacidosis are associated with increased rates of perinatal morbidity and mortality. A high index of suspicion is required, because diabetic ketoacidosis onset in pregnancy can be insidious, usually at lower glucose levels, and often progresses more rapidly as compared with nonpregnancy. Morbidity and mortality can be reduced with early detection of precipitating factors (ie, infection, intractable vomiting, inadequate insulin management or inappropriate insulin cessation, &bgr;-sympathomimetic use, steroid administration for fetal lung maturation), prompt hospitalization, and targeted therapy with intensive monitoring. A multidisciplinary approach including a maternal-fetal medicine physician, medical endocrinology specialists familiar with the physiologic changes in pregnancy, an obstetric anesthesiologist, and skilled nursing is paramount. Management principles include aggressive volume replacement, initiation of intravenous insulin therapy, correction of acidosis, correction of electrolyte abnormalities and management of precipitating factors, as well as monitoring of maternal-fetal response to treatment. When diabetic ketoacidosis occurs after 24 weeks of gestation, fetal status should be continuously monitored given associated fetal hypoxemia and acidosis. The decision for delivery can be challenging and must be based on gestational age as well as maternal-fetal responses to therapy. The natural inclination is to proceed with emergent delivery for nonreassuring fetal status that is frequently present during the acute episode, but it is imperative to correct the maternal metabolic abnormalities first, because both maternal and fetal conditions will likewise improve. Prevention strategies should include education of diabetic pregnant women about the risks of diabetic ketoacidosis, precipitating factors, and the importance of reporting signs and symptoms in a timely fashion.

Fetal Anomalies and Long-Term Effects Associated with Substance Abuse in Pregnancy: A Literature Review

OBJECTIVES Substance abuse in pregnancy remains a major public health problem. Fetal teratogenicity results from the effect of these substances during fetal development, particularly when used in combination. This review will focus on and attempt to clarify the existing literature regarding the association of substance abuse on the development of congenital anomalies and the long-term implications in exposed offspring. METHODS Systematic review of available English literature using the PubMed database of all peer-reviewed articles on the subject. RESULTS A total of 128 articles were included in this review. Alcohol was the most common substance associated with fetal anomalies, particularly facial dysmorphisms and alterations in the central nervous system development. Adverse maternal environments associated with risky behaviors and lack of adequate prenatal care precludes the timely detection of fetal anomalies, confounding most studies linking causality. In addition, although methodological differences and limited availability of well-designed trials exist, substance abuse in pregnancy has been associated with adverse long-term outcomes in infant growth, behavior, cognition, language and achievement. CONCLUSION The literature summarized in this review suggests that drug exposure during pregnancy may increase the risk of congenital anomalies and long-term adverse effects in exposed children and adolescents. These conclusions must be tempered by the many confounders associated with drug use. A multidisciplinary approach is paramount for appropriate counseling regarding the known immediate and long-term risks of substance abuse in pregnancy.

Antenatal Corticosteroids for the Prevention of Respiratory Distress Syndrome in Premature Twins.

OBJECTIVE: To estimate whether antenatal corticosteroids before 34 weeks of gestation are associated with reduced incidence of respiratory distress syndrome (RDS) and composite neonatal morbidity in preterm twins. METHODS: This was a secondary analysis of a multicenter randomized trial for the prevention of preterm birth in multiple gestations. All liveborn, nonanomalous twins delivered between 24 0/7 and 36 6/7 weeks of gestation were included. Neonatal outcomes were compared between women who received antenatal corticosteroids and those who did not. The primary outcome was the incidence of RDS. The secondary outcome was the incidence of serious composite neonatal morbidity. Multivariable log Poisson regression with correlation adjustment between twins born to the same mother was performed for confounder control. Adjusted relative risks (RRs) are reported for study outcomes. Based on a post hoc power analysis, this study was powered to detect an RR less than 0.63 for RDS and greater than 1.43 for composite neonatal morbidity outcomes. RESULTS: A total of 432 women (850 neonates) were included. Only 300 (35%) neonates were born to women receiving antenatal corticosteroids. After multivariable regression, antenatal corticosteroids were not associated with a reduced incidence of RDS (81 [27%] compared with 92 [17%] neonates, adjusted RR 1.28, 95% confidence interval [CI] 0.97–1.71) or composite neonatal morbidity (87 [29%] compared with 108 [20%] neonates, adjusted RR 1.21, 95% CI 0.93–1.56). However, antenatal corticosteroids were associated with increased rates of neonatal intensive care unit admissions (235 [78%] compared with 322 [59%] neonates, adjusted RR 1.22, 95% CI 1.09–1.36) and mechanical ventilation (70 [23%] compared with 66 [12%] neonates, adjusted RR 1.52, 95% CI 1.12–2.09). Focusing analysis to newborns delivered before 34 weeks of gestation (n=311), 161 (52%) received antenatal corticosteroids. Similarly, no differences in the rate of RDS (66 [41%] compared with 68 [45%] neonates, adjusted RR 1.01, 95% CI 0.76–1.34) or composite neonatal morbidity (72 [45%] compared with 81 [54%] neonates, adjusted RR 0.95, 95% CI 0.74–1.22) were noted. CONCLUSION: In this cohort of preterm twins, antenatal corticosteroid administration was not associated with a reduced incidence of RDS and composite neonatal morbidity.

Neonatal and infant outcomes in twin gestations with preterm premature rupture of membranes at 24-31 weeks of gestation.

OBJECTIVE: To describe the perinatal and infant and early childhood morbidity associated with preterm premature rupture of membranes (PROM) in a cohort of twin pregnancies evaluated prospectively with neonatal follow-up to 2 years of age. METHODS: This was a secondary analysis of a randomized controlled trial of magnesium sulfate for prevention of cerebral palsy. Inclusion criteria were twin gestation with preterm PROM diagnosed between 24 0/7 and 31 6/7 weeks of gestation and planned expectant management. Latency (time from membrane rupture to delivery) and perinatal outcomes were evaluated by gestational age at membrane rupture. Long-term neonatal outcomes were also analyzed. RESULTS: Among 151 women who met inclusion criteria, the median gestational age at preterm PROM was 28.1 weeks (range 24.1–31.6 weeks). Approximately one-third of women achieved a latency of at least 1 week. Gestational age at preterm PROM (odds ratio [OR] 0.75, 95% confidence interval [CI] 0.63–0.90 for each week after 24 weeks of gestation) and cervical dilation at admission (OR 0.66, 95% CI 0.49–0.90 for each centimeter of dilation) were inversely associated with a latency period of at least 1 week. There were no stillbirths (95% CI 0–1%), but the rate of neonatal mortality was 90 per 1,000 newborns (95% CI 57–112) with a 7.3% cerebral palsy rate among survivors (95% CI 4.4–10.3%). CONCLUSION: In twin pregnancies, preterm PROM from 24 to 31 weeks of gestation is associated with a neonatal mortality rate of 9.0% and an overall cerebral palsy rate of 7.3%. A longer latency period is associated with less advanced cervical dilation and later gestational age at PROM. LEVEL OF EVIEDENCE: II

A Rapidly Growing Abdominal Mass: Desmoid Tumor in Pregnancy

Background Desmoid tumors are benign soft tissue tumors that locally invade adjacent tissue. There is a paucity of reports describing the rapid growth of these tumors during pregnancy. Case A giant desmoid tumor arising from the left abdominal wall of a young female patient with rapid growth during pregnancy is described. Preoperative evaluation included ultrasonography and magnetic resonance imaging. Decision made by a multidisciplinary team was not to intervene before birth, and abdominal delivery at term was accomplished. Conclusion Desmoid tumors should be part of the differential diagnosis in an abdominal wall tumor of rapid growth during pregnancy. Future studies are needed for better understanding of the pathogenesis, diagnosis, and treatment of desmoid tumors in pregnant women.

Relationship between Self-Reported Maternal Substance Abuse and Adverse Outcomes in the Premature Newborn

OBJECTIVE This study aims to compare neonatal and long-term outcomes among preterm newborns from women with reported versus those who did not report substance abuse. STUDY DESIGN Secondary analysis of a trial of magnesium sulfate for cerebral palsy prevention. Cases were pregnant women who reported substance abuse, controls were those who denied it. Study outcomes included (1) composite neonatal morbidity, defined as any of the following: Apgar score ≤ 3 at 5 minutes, seizures, culture-proven sepsis, necrotizing enterocolitis grades 2 or 3, intraventricular hemorrhage grades 3 or 4, and/or death before discharge; (2) infant and childhood morbidity, defined as stillbirth or death by 1 year, or moderate/severe cerebral palsy by age of 2. RESULTS Among 1,972 women meeting the inclusion criteria, 197 (10%) reported substance abuse. Composite neonatal, infant, and childhood morbidity rates were similar between cases and controls. However, women reporting substance abuse who delivered between 32(0/7) and 36(6/7) weeks had a higher frequency of composite infant and childhood morbidity (6.5 vs. 1.0%; adjusted odds ratio, 6.5; 95% confidence interval, 1.14-36.99). CONCLUSIONS Preterm birth was associated with similar composite neonatal morbidity between cases and controls. After 32 weeks, self-reported substance abuse was associated with a sevenfold increase in the rates of stillbirth and long-term infant morbidity.

Association of Nonsteroidal Antiinflammatory Drugs and Postpartum Hypertension in Women With Preeclampsia With Severe Features.

OBJECTIVE To estimate whether nonsteroidal antiinflammatory drugs (NSAIDs) are associated with persistent postpartum hypertension in a cohort of women with preeclampsia and severe features. METHODS We conducted a retrospective cohort study at a single, tertiary center from January 2013 to December 2015. All women diagnosed with severe preeclampsia who remained hypertensive for greater than 24 hours after delivery were included. The primary outcome was the rate of persistent postpartum hypertension, defined as systolic blood pressure 150 mm Hg or greater or diastolic 100 mm Hg or greater (or both), on two occasions, at least 4 hours apart. Secondary outcomes included severe maternal morbidity: pulmonary edema, renal dysfunction, stroke, eclampsia, and intensive care unit admission. Additional outcomes included length of postpartum hospital stay, receipt of narcotics, and hospital readmission. Multivariable logistic regression was performed to adjust for confounders. Adjusted odds ratios (ORs) are reported for applicable study outcomes. RESULTS Of the 399 women with severe preeclampsia, 324 (81%) remained hypertensive 24 hours after delivery. Two hundred forty-three (75%) received NSAIDs (either ibuprofen or ketorolac) and 81 (25%) did not. After multivariable logistic regression, the likelihood of reaching a blood pressure of 150 mm Hg systolic or 100 mm Hg diastolic (or both), on two occasions, at least 4 hours apart, was similar between those who received NSAIDs compared with those who did not (70% compared with 73%; adjusted OR 1.1, 95% CI 0.6-2.0). Similarly, puerperal occurrence of pulmonary edema (3% compared with 10%; OR 4.4, 95% CI 1.5-13.1), renal dysfunction (5% compared with 8%; OR 1.7, 95% CI 0.6-4.8), eclampsia (1% compared with 0%; P=.34), or intensive care unit admission (3% compared with 8%; OR 2.4, 95% CI 0.8-7.1) was similar between the groups. There were no differences in the rate of narcotic use (89% compared with 75%; adjusted OR 0.6 95% CI 0.18-1.70). CONCLUSION In this cohort of women with preeclampsia and severe features before delivery, NSAIDs were not associated with increased rates of persistent postpartum hypertension.

Potential of Metformin to Improve Cardiac Risk in Postpartum Women with Gestational Diabetes

Objective Pregnancy is associated with an increase in total cholesterol, high density lipoproteins (HDL), and low-density lipoproteins (LDL). Postpartum, HDL and LDL decrease over the first 12 weeks postpartum. Oxidized LDL (ox-LDL) is a marker of oxidative stress-related inflammation, which is associated with obesity and also with development of cardiovascular disease. Cardiovascular protection and weight loss are benefits from metformin, especially in women with diabetes. The objective of this study was to compare changes in lipid profiles and biomarkers for obesity during the initial 6 weeks postpartum between women with gestational diabetes mellitus (GDM) treated with metformin versus placebo. Methods This was a planned ancillary study of a randomized controlled trial compares metformin versus placebo in women with GDM for postpartum weight loss. Two 3 mL blood samples were collected within 24 h of delivery and 6 weeks postpartum immediately processed after collection then stored at −20°C until completion of clinical trial prior to analysis. Change in the median plasma concentrations of total cholesterol, HDL, ox-LDL, glucose, insulin, leptin, and unacylated ghrelin were compared between study groups. Results Of the 77 postpartum women were included, 35 received metformin and 42 received placebo. There was less of a reduction in HDL in the metformin group compared to placebo (−2.3 versus −7.5 mg/dL, p = 0.019). In addition, there was a greater reduction in ox-LDL in those receiving metformin (−12.2 versus −3.8 mg/dL, p = 0.038). No other differences were observed in the selected biomarkers evaluated. Conclusion Biomarker levels of HDL and ox-LDL were positively affected during the initial 6 weeks postpartum in GDM women treated with metformin. Additional studies with a longer duration of metformin treatment in the postpartum period are warranted to evaluate long-term potential benefits.

Timing of Medically Indicated Delivery in Diabetic Pregnancies: A Perspective on Current Evidence-Based Recommendations

Diabetes complicates 6 to 7% of all pregnancies in the United States. Poor glycemic control is associated with multiple immediate and long-term adverse effects on both the mother and fetus. Although uniformity exists in the antenatal management of this disease, there is a paucity of evidence-based studies upon which to dictate the optimal time of delivery among affected women. The potential risks of delayed neonatal pulmonary maturation including respiratory distress syndrome and transient tachypnea of the newborn associated with early delivery must be balanced with the increased incidence of fetal demise, overgrowth, and birth injury related to diabetes in late gestations. Even among diabetic women with optimal glycemic control, the risk of stillbirth in the third trimester is considerably higher than their normal counterparts. The current paradigm of delaying delivery to 39 weeks in women with controlled and uncomplicated diabetes has been challenged by recent evidence advocating delivery by 38 weeks to improve perinatal outcomes. However, additional well-designed and adequately powered prospective studies are needed to better understand the short- and long-term implications of the optimal timing of delivery in this high-risk population. This article reviews the most current literature regarding the optimal timing of delivery in pregnancies complicated by diabetes mellitus and gestational diabetes mellitus.

Twin gestation in a Swyer syndrome patient with superimposed pre-eclampsia

Jaimin S. Shah , Oscar A. Viteri, Monica Longo, Mazen Abdallah and Baha Sibai Department of Obstetrics, Gynecology and Reproductive Sciences, The University of Texas at Houston McGovern Medical School, Houston, TX, USA; Department of Maternal-Fetal Medicine, The University of Texas at Houston McGovern Medical School, Houston, TX, USA; Department of Reproductive, Endocrinology and Infertility, The University of Texas at Houston McGovern Medical School, Houston, TX, USA