Putting the "M" back in maternal-fetal medicine: A 5-year report card on a collaborative effort to address maternal morbidity and mortality in the United States.

The Centers for Disease Control and Prevention have demonstrated continuous increased risk for maternal mortality and severe morbidity with racial disparities among non-Hispanic black women an important contributing factor. More than 50,000 women experienced severe maternal morbidity in 2014, with a mortality rate of 18.0 per 100,000, higher than in many other developed countries. In 2012, the first "Putting the 'M' back in Maternal-Fetal Medicine" session was held at the Society for Maternal-Fetal Medicine's (SMFM) Annual Meeting. With the realization that rising risk for severe maternal morbidity and mortality required action, the "M in MFM" meeting identified the following urgent needs: (i) to enhance education and training in maternal care for maternal-fetal medicine (MFM) fellows; (ii) to improve the medical care and management of pregnant women across the country; and (iii) to address critical research gaps in maternal medicine. Since that first meeting, a broad collaborative effort has made a number of major steps forward, including the proliferation of maternal mortality review committees, advances in research, increasing educational focus on maternal critical care, and development of comprehensive clinical strategies to reduce maternal risk. Five years later, the 2017 M in MFM meeting served as a "report card" looking back at progress made but also looking forward to what needs to be done over the next 5 years, given that too many mothers still experience preventable harm and adverse outcomes.

Maternal-Fetal Medicine Workforce Survey: Are We Ready for Regionalized Levels of Maternal Care?

OBJECTIVE: To conduct a survey of the members of the Society for Maternal-Fetal Medicine (SMFM) to determine the practice patterns of maternal-fetal medicine (MFM) subspecialists in the United States and to estimate the likelihood that our work force is sufficient to support the proposed MFM staffing requirements for level III and IV maternity centers. STUDY DESIGN: All regular SMFM members in the United States were invited to answer a 26 question survey by email. The survey queried demographic characteristics, practice type, night call arrangements, and whether the respondent's hospital was currently equipped with the services and personnel described in the requirements for level III or IV centers. RESULTS: Of the MFM specialists working full time in what would be considered a level III or IV maternity center, only 47.5% took in-house call. Of those taking only call from home or back-up call, the majority reported that during call hours, MFM antepartum and laboring patients are cared for by generalist obstetrician gynecologists; only 6.4% work with MFM hospitalists. Respondents from level III or IV centers also reported that many of their centers did not meet the criteria for nursing support, anesthesia support, or intensive care services. CONCLUSION: These data, if confirmed, indicate that work needs to be done to upgrade services and achieve appropriate staffing to meet the proposed level III and IV criteria for maternity care.

Malignancies in pregnancy.

Malignancy complicating pregnancy is fortunately rare, affecting one in 1000 to one in 1500 pregnancies. Optimal treatment involves balancing the benefit of treatment for the mother while minimizing harm to the fetus. This balance is dependent on the extent of the disease, the recommended course of treatment, and the gestational age at which treatment is considered. Both surgery and chemotherapy are generally safe in pregnancy, whereas radiation therapy is relatively contraindicated. Iatrogenic prematurity is the most common pregnancy complication, as infants are often delivered for maternal benefit. In general, however, survival does not differ from the nonpregnant population. These patients require a multidisciplinary approach for management with providers having experience in caring for these complex patients. The aim of this review was to provide an overview for obstetricians of the diagnosis and management of malignancy in pregnancy.

Perinatal outcomes with normal compared with elevated umbilical artery systolic-to-diastolic ratios in fetal growth restriction.

OBJECTIVE: To compare the composite neonatal morbidity of pregnancies with fetal growth restriction (estimated fetal weight less than the 10th percentile) and normal compared with elevated umbilical artery systolic-to-diastolic ratios. METHODS: This was a retrospective cohort study of all pregnancies complicated by fetal growth restriction with normal compared with elevated umbilical artery systolic-to-diastolic ratios from January 2008 to July 2012 at a single center. Exclusions were multiple gestation, prenatally diagnosed fetal anomalies, delivery at outside institution, and absent or reversed end diastolic flow. Maternal characteristics and perinatal outcomes including composite neonatal morbidity were compared between groups. RESULTS: Of 11,785 pregnancies evaluated, 789 (7%) were diagnosed with fetal growth restriction. Among 512 that met inclusion criteria, 394 (77%) had normal and 118 (23%) had elevated umbilical artery systolic-to-diastolic ratios. When fetal growth-restricted pregnancies with elevated umbilical artery systolic-to-diastolic ratios were delivered at 37 weeks of gestation were compared with those with normal umbilical artery systolic-to-diastolic ratios delivered at 39 weeks of gestation, there was no difference in the rate of neonatal intensive care unit admission (101 [25.7%] compared with 51 [43.2%]; crude odds ratio [OR] 2.5, 95% confidence interval 1.5-4.0; adjusted OR 1.37, 95% CI 0.69-2.71) or composite neonatal morbidity (60 [15.2%] compared with 24 [20.3%]; crude OR 1.42, 95% CI 0.84-2.40; adjusted OR 0.91, 95% CI 0.45-1.84). CONCLUSION: Composite neonatal morbidity is comparable in fetal growth-restricted pregnancies with elevated compared with normal umbilical artery systolic-to-diastolic ratios when delivered at 37 and 39 weeks of gestation, respectively. Planning delivery of pregnancies with fetal growth restriction and elevated systolic-to-diastolic ratios and without other complications at 37 weeks of gestation results in good outcomes.

Early term versus term delivery in the management of fetal growth restriction: a comparison of two protocols.

OBJECTIVE: This study aims to compare two management protocols in pregnancies diagnosed with fetal growth restriction (FGR). STUDY DESIGN: All singleton pregnancies diagnosed and managed with FGR at our institution during two protocol periods were analyzed. The early term protocol (January 2008-February 2010) specified delivery at 37(0/7) weeks if antenatal testing was reassuring, but did not specify the timing of delivery if umbilical artery (UA) Doppler systolic:diastolic (S:D) ratios were elevated (>95th percentile for gestational age [GA]). The term protocol (March 2010-July 2012) specified delivery at 39(0/7) weeks with normal S:D ratios and 37(0/7) weeks with elevated S:D ratios when antenatal testing was reassuring. RESULTS: There were 228 and 312 women in the early term and term protocol, respectively, who met inclusion criteria. Compared with the early term group, the term group had an increased median GA at delivery (37.1 vs. 38.6%, p < 0.001), decreased deliveries less than 37(0/7) weeks (37 vs. 24%, p = 0.01) and decreased neonatal intensive care unit (NICU) admissions (38 vs. 28%, p = 0.02). CONCLUSION: A protocol specifying delivery at 39(0/7) weeks when UA S:D ratios are normal and delivery at 37(0/7) weeks when UA S:D ratios are elevated when other antenatal testing is reassuring in FGR: (1) prolonged gestation, (2) decreased preterm births, and (3) decreased NICU admissions.

Fetal surgery: principles, indications, and evidence.

Since the first human fetal surgery was reported in 1965, several different fetal surgical procedures have been developed and perfected, resulting in significantly improved outcomes for many fetuses. The currently accepted list of fetal conditions for which antenatal surgery is considered include lower urinary tract obstruction, twin-twin transfusion syndrome, myelomeningocele, congenital diaphragmatic hernia, neck masses occluding the trachea, and tumors such as congenital cystic adenomatoid malformation or sacrococcygeal teratoma when associated with developing fetal hydrops. Until recently, it has been difficult to determine the true benefits of several fetal surgeries because outcomes were reported as uncontrolled case series. However, several prospective randomized trials have been attempted and others are ongoing, supporting a more evidence-based approach to antenatal intervention. Problems that have yet to be completely overcome include the inability to identify ideal fetal candidates for antenatal intervention, to determine the optimal timing of intervention, and to prevent preterm birth after fetal surgery. Confronting a fetal abnormality raises unique and complex issues for the family. For this reason, in addition to a maternal-fetal medicine specialist experienced in prenatal diagnosis, a pediatric surgeon, an experienced operating room team including a knowledgeable anesthesiologist, and a neonatologist, the family considering fetal surgery should have access to psychosocial support and a bioethicist.

The FDA's new advice on fish: it's complicated.

The Food and Drug Administration and Environmental Protection Agency recently issued an updated draft of advice on fish consumption for pregnant and breastfeeding women, after survey data indicated that the majority of pregnant women do not eat much fish and thus may have inadequate intake of the omega 3 fatty acids eicosapentaenoic acid [EPA] and ducosahexaenoic acid [DHA]. Omega 3 fatty acids are essential components of membranes in all cells of the body and are vitally important for normal development of the brain and retinal tissues (especially myelin and retinal photoreceptors) and for maintenance of normal neurotransmission and connectivity. They also serve as substrates for the synthesis of a variety of antiinflammatory and inflammation-resolving mediators, favorably alter the production of thromboxane and prostaglandin E2, and improve cardiovascular health by preventing fatal arrhythmias and reducing triglyceride and C-reactive protein levels. Maternal ingestion of adequate quantities of fish (defined in many studies as at least 340 g of oily fish each week) has been associated with better childhood IQ scores, fine motor coordination, and communication and social skills, along with other benefits. Although the FDA did not clarify which fish to eat, it specifically advised against eating fish with the highest mercury levels and implied that fish with high levels of EPA and DHA and low levels of mercury are ideal. The FDA draft did not recommend taking omega 3 fatty acid or fish oil supplements instead of eating fish, which is advice that may reflect the fact that randomized controlled trials of DHA and EPA or fish oil supplementation generally have been disappointing and that the ideal daily dose of DHA and EPA is unknown. It seems safe to conclude that pregnant and nursing women should be advised to eat fish to benefit from naturally occurring omega 3 fatty acids, to avoid fish with high levels of mercury and other contaminants, and, if possible, to choose fish with high levels of EPA and DHA.

Preventing the first cesarean delivery: summary of a joint Eunice Kennedy Shriver National Institute of Child Health and Human Development, Society for Maternal-Fetal Medicine, and American College of Obstetricians and Gynecologists Workshop.

With more than one third of pregnancies in the United States being delivered by cesarean and the growing knowledge of morbidities associated with repeat cesarean deliveries, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the Society for Maternal-Fetal Medicine, and the American College of Obstetricians and Gynecologists convened a workshop to address the concept of preventing the first cesarean delivery. The available information on maternal and fetal factors, labor management and induction, and nonmedical factors leading to the first cesarean delivery was reviewed as well as the implications of the first cesarean delivery on future reproductive health. Key points were identified to assist with reduction in cesarean delivery rates including that labor induction should be performed primarily for medical indication; if done for nonmedical indications, the gestational age should be at least 39 weeks or more and the cervix should be favorable, especially in the nulliparous patient. Review of the current literature demonstrates the importance of adhering to appropriate definitions for failed induction and arrest of labor progress. The diagnosis of "failed induction" should only be made after an adequate attempt. Adequate time for normal latent and active phases of the first stage, and for the second stage, should be allowed as long as the maternal and fetal conditions permit. The adequate time for each of these stages appears to be longer than traditionally estimated. Operative vaginal delivery is an acceptable birth method when indicated and can safely prevent cesarean delivery. Given the progressively declining use, it is critical that training and experience in operative vaginal delivery are facilitated and encouraged. When discussing the first cesarean delivery with a patient, counseling should include its effect on future reproductive health.

First-trimester Down syndrome screening: component analytes and timing for optimal performance.

The most effective first-trimester Down syndrome screening protocol in current use employs three independent markers: maternal serum levels of PAPP-A and free beta hCG, and measurement of fetal nuchal translucency (NT). Eleven weeks appears to be the optimum gestational age for performing first trimester DS risk assessment. Although the discrimination of free beta hCG improves with increasing gestational age and is greatest at 13 weeks, PAPP-A and NT perform optimally at 10 and 11 weeks, respectively. In addition to accurate pregnancy dating, first trimester screening performance is improved by using a consistent NT measurement technique, NT cut-offs adjusted for gestational age or crown-rump length, and possibly center- or operator-specific NT medians. Whether or not absence or presence of the nasal bone adds to screening accuracy is a matter of some debate. Finally, because enlarged NT has been associated with cardiac defects and other structural anomalies, even in euploid fetuses, its presence should prompt a targeted second trimester ultrasound examination.

Evaluation of Down syndrome screening strategies.

Women contemplating pregnancy today have many different Down syndrome screening protocols from which to choose. Sensitive and specific first and second trimester screening protocols are now widely available, and strategies that combine first and second trimester markers are moving from investigational use into the clinical arena. Modeling indicates that a high detection rate (85%) associated with a very low screen positive rate (1.3%) can be achieved with contingent screening, in which all women undergo first trimester screening and only a portion (25%) go on to second trimester screening.

Midtrimester amniotic fluid matrix metalloproteinase-8 (MMP-8) levels above the 90th percentile are a marker for subsequent preterm premature rupture of membranes.

OBJECTIVE: We sought to determine whether midtrimester amniotic fluid levels of matrix metalloproteinase-8 were associated with subsequent preterm premature rupture of membranes. STUDY DESIGN: We conducted a case-control study examining 57 asymptomatic women who underwent genetic amniocentesis from 14 to 21 weeks' gestation and subsequently had preterm premature rupture of membranes (<35 wk) and 58 women with subsequent term delivery. Measurement of total matrix metalloproteinase-8 level in amniotic fluid was conducted using a commercially available enzyme-linked immunosorbent assay and association with preterm birth due to preterm premature rupture of membranes was assessed. RESULTS: The overall distribution of matrix metalloproteinase-8 concentrations was similar in women who had preterm premature rupture of membranes and term controls (median 2.39 ng/mL, 25th to 75th percentile 1.1-10.1 vs 2.37 ng/mL, 25th to 75th percentile 1.5-4.7, P = .94). However, 26% of women who had preterm premature rupture of membranes had a matrix metalloproteinase-8 concentration above the 90th percentile (8.7 ng/mL), compared with only 10% of term controls (odds ratio 3.1, 95% CI 1.1-8.7; P = .03). Elevated matrix metalloproteinase-8 remained associated with preterm premature rupture of membranes after adjustment for maternal age, race, parity, gestational age, and year of amniocentesis (odds ratio 3.4, 95% CI 1.2-9.9; P = .03). CONCLUSIONS: The overall distribution of midtrimester amniotic fluid matrix metalloproteinase-8 levels did not differ between women who had preterm premature rupture of membranes and those delivered at term. However, marked elevations of midtrimester amniotic fluid matrix metalloproteinase-8 were highly associated with subsequent preterm premature rupture of membranes, suggesting that the pathophysiologic processes that contribute to preterm premature rupture of membranes may begin in early pregnancy.

Fetal open spina bifida: a natural history of disease progression in utero.

OBJECTIVE: To determine the natural history of the prenatal development of ventriculomegaly and talipes in fetuses with open spina bifida. STUDY DESIGN: All fetuses with isolated open spina bifida and managed at our center between January 1996 and March 2000 were retrospectively evaluated. Ultrasonographic images and reports were reviewed from examinations performed every 3 to 4 weeks from the time of diagnosis to delivery for lesion level and type, ventriculomegaly (defined as an atrial width of > or =10 mm), and lower extremity appearance. RESULTS: Of the 53 pregnancies identified, 20 (38%) were electively terminated. In the 33 ongoing gestations, the lesions ranged from lower thoracic to sacral; 79% were characterized as meningomyeloceles and 21% as myeloschises. Fifty-five percent (n = 18) had ventriculomegaly at diagnosis (early onset, mean gestational age at diagnosis 22 +/- 5 weeks), 33% (n = 11) subsequently developed ventriculomegaly (late onset, mean 29 +/- 6 weeks), and 12% (n = 4) had normal ventricle size at the last sonogram before birth (mean 38 +/- 1 weeks). The ventricular size prior to delivery was significantly smaller with late-onset ventriculomegaly than with early-onset: 15 +/- 4 mm versus 28 +/- 10 mm, (p = 0.001). Only 6% (n = 2) had talipes at the initial sonogram, and 18% (n = 6) were subsequently determined to have talipes (mean 30 +/- 6 weeks). CONCLUSION: Most fetuses with open spina bifida develop ventriculomegaly, and the majority do so by 21 weeks' gestation. Fetuses that develop ventriculomegaly later in gestation have less severe ventricular dilation at birth. In contrast, a minority of fetuses have congenital talipes, and because most cases develop after 20 weeks, they are not predicted by early midtrimester sonographic evaluation.

Fragile X and other trinucleotide repeat diseases.

Hereditary unstable DNA is composed of strings of trinucleotide repeats, in which three nucleotides are repeated over and over (ie CAGCAGCAGCAG). These repeats are found in several sites within genes; depending on their location, the number of triplet repeats in a string can change as it is passed on to offspring. When the number of repeats increases to a critical size, it can have a variety of affects on gene function. The repeats may cause a loss in gene function (as in Fragile X) or may result in the gain of a new, abnormal protein and thus a new function (as in myotonic dystrophy and Huntington disease). Although a variety of trinucleotide repeat diseases have been reported and merit consideration, this discussion will focus primarily on Fragile X syndrome, myotonic dystrophy, and Huntington disease.