Multiethnic growth standards for fetal body composition and organ volumes derived from 3D ultrasonography.

BACKGROUND: A major goal of contemporary obstetrical practice is to optimize fetal growth and development throughout pregnancy. To date, fetal growth during prenatal care is assessed by performing ultrasonographic measurement of 2-dimensional fetal biometry to calculate an estimated fetal weight. Our group previously established 2-dimensional fetal growth standards using sonographic data from a large cohort with multiple sonograms. A separate objective of that investigation involved the collection of fetal volumes from the same cohort. OBJECTIVE: The Fetal 3D Study was designed to establish standards for fetal soft tissue and organ volume measurements by 3-dimensional ultrasonography and compare growth trajectories with conventional 2-dimensional measures where applicable. STUDY DESIGN: The National Institute of Child Health and Human Development Fetal 3D Study included research-quality images of singletons collected in a prospective, racially and ethnically diverse, low-risk cohort of pregnant individuals at 12 U.S. sites, with up to 5 scans per fetus (N=1730 fetuses). Abdominal subcutaneous tissue thickness was measured from 2-dimensional images and fetal limb soft tissue parameters extracted from 3-dimensional multiplanar views. Cerebellar, lung, liver, and kidney volumes were measured using virtual organ computer aided analysis. Fractional arm and thigh total volumes, and fractional lean limb volumes were measured, with fractional limb fat volume calculated by subtracting lean from total. For each measure, weighted curves (fifth, 50th, 95th percentiles) were derived from 15 to 41 weeks' using linear mixed models for repeated measures with cubic splines. RESULTS: Subcutaneous thickness of the abdomen, arm, and thigh increased linearly, with slight acceleration around 27 to 29 weeks. Fractional volumes of the arm, thigh, and lean limb volumes increased along a quadratic curvature, with acceleration around 29 to 30 weeks. In contrast, growth patterns for 2-dimensional humerus and femur lengths demonstrated a logarithmic shape, with fastest growth in the second trimester. The mid-arm area curve was similar in shape to fractional arm volume, with an acceleration around 30 weeks, whereas the curve for the lean arm area was more gradual. The abdominal area curve was similar to the mid-arm area curve with an acceleration around 29 weeks. The mid-thigh and lean area curves differed from the arm areas by exhibiting a deceleration at 39 weeks. The growth curves for the mid-arm and thigh circumferences were more linear. Cerebellar 2-dimensional diameter increased linearly, whereas cerebellar 3-dimensional volume growth gradually accelerated until 32 weeks followed by a more linear growth. Lung, kidney, and liver volumes all demonstrated gradual early growth followed by a linear acceleration beginning at 25 weeks for lungs, 26 to 27 weeks for kidneys, and 29 weeks for liver. CONCLUSION: Growth patterns and timing of maximal growth for 3-dimensional lean and fat measures, limb and organ volumes differed from patterns revealed by traditional 2-dimensional growth measures, suggesting these parameters reflect unique facets of fetal growth. Growth in these three-dimensional measures may be altered by genetic, nutritional, metabolic, or environmental influences and pregnancy complications, in ways not identifiable using corresponding 2-dimensional measures. Further investigation into the relationships of these 3-dimensional standards to abnormal fetal growth, adverse perinatal outcomes, and health status in postnatal life is warranted.

Society for Maternal-Fetal Medicine Consult Series #64: Systemic lupus erythematosus in pregnancy.

Systemic lupus erythematosus (SLE) is a chronic, multisystem, inflammatory autoimmune disease characterized by relapses (commonly called "flares") and remission. Many organs may be involved, and although the manifestations are highly variable, the kidneys, joints, and skin are commonly affected. Immunologic abnormalities, including the production of antinuclear antibodies, are also characteristic of the disease. Maternal morbidity and mortality are substantially increased in patients with systemic lupus erythematosus, and an initial diagnosis of systemic lupus erythematosus during pregnancy is associated with increased morbidity. Common complications of systemic lupus erythematosus include nephritis, hematologic complications such as thrombocytopenia, and a variety of neurologic abnormalities. The purpose of this document is to examine potential pregnancy complications and to provide recommendations on treatment and management of systemic lupus erythematosus during pregnancy. The following are the Society for Maternal-Fetal Medicine recommendations: (1) we recommend low-dose aspirin beginning at 12 weeks of gestation until delivery in patients with systemic lupus erythematosus to decrease the occurrence of preeclampsia (GRADE 1B); (2) we recommend that all patients with systemic lupus erythematosus, other than those with quiescent disease, either continue or initiate hydroxychloroquine (HCQ) in pregnancy (GRADE 1B); (3) we suggest that for all other patients with quiescent disease activity who are not taking HCQ or other medications, it is reasonable to engage in shared decision-making regarding whether to initiate new therapy with this medication in consultation with the patient's rheumatologist (GRADE 2B); (4) we recommend that prolonged use (>48 hours) of nonsteroidal antiinflammatory drugs (NSAIDs) generally be avoided during pregnancy (GRADE 1A); (5) we recommend that COX-2 inhibitors and full-dose aspirin be avoided during pregnancy (GRADE 1B); (6) we recommend discontinuing methotrexate 1-3 months and mycophenolate mofetil/mycophenolic acid at least 6 weeks before attempting pregnancy (GRADE 1A); (7) we suggest the decision to initiate, continue, or discontinue biologics in pregnancy be made in collaboration with a rheumatologist and be individualized to the patient (GRADE 2C); (8) we suggest treatment with a combination of prophylactic unfractionated or low-molecular-weight heparin and low-dose aspirin for patients without a previous thrombotic event who meet obstetrical criteria for antiphospholipid syndrome (APS) (GRADE 2B); (9) we recommend therapeutic unfractionated or low-molecular-weight heparin for patients with a history of thrombosis and antiphospholipid (aPL) antibodies (GRADE 1B); (10) we suggest treatment with low-dose aspirin alone in patients with systemic lupus erythematosus and antiphospholipid antibodies without clinical events meeting criteria for antiphospholipid syndrome (GRADE 2C); (11) we recommend that steroids not be routinely used for the treatment of fetal heart block due to anti-Sjögren's-syndrome-related antigen A or B (anti-SSA/SSB) antibodies given their unproven benefit and the known risks for both the pregnant patient and fetus (GRADE 1C); (12) we recommend that serial fetal echocardiograms for assessment of the PR interval not be routinely performed in patients with anti-SSA/SSB antibodies outside of a clinical trial setting (GRADE 1B); (13) we recommend that patients with systemic lupus erythematosus undergo prepregnancy counseling with both maternal-fetal medicine and rheumatology specialists that includes a discussion regarding maternal and fetal risks (GRADE 1C); (14) we recommend that pregnancy be generally discouraged in patients with severe maternal risk, including patients with active nephritis; severe pulmonary, cardiac, renal, or neurologic disease; recent stroke; or pulmonary hypertension (GRADE 1C); (15) we recommend antenatal testing and serial growth scans in pregnant patients with systemic lupus erythematosus because of the increased risk of fetal growth restriction (FGR) and stillbirth (GRADE 1B); and (16) we recommend adherence to the Centers for Disease Control and Prevention medical eligibility criteria for contraceptive use in patients with systemic lupus erythematosus (GRADE 1B).

Identification of micrognathia by prenatal ultrasound may improve timely diagnosis and management of infants with Robin sequence.

OBJECTIVE: Robin sequence (RS) is a craniofacial anomaly characterized by small jaw (micrognathia) with associated tongue base airway obstruction. With advances in fetal imaging, micrognathia may be detected prenatally. This study aims to determine if prenatal recognition of micrognathia offers any advantage over being unaware of the condition until after delivery and to assess if prenatal consultation for micrognathia adds benefits beyond merely noting the presence of the condition. METHOD: Retrospective chart review examining cases from 01/01/2010 to 12/31/2020 at an urban tertiary medical center. RESULTS: Forty seven infants with RS were included. 40.4% (n = 19) had micrognathia/retrognathia noted on prenatal ultrasound. 47.4% (n = 9) of those 19 pregnancies saw a maternal fetal medicine (MFM) program with craniofacial consultation. Compared to 28 infants not diagnosed with micrognathia until after birth, the 19 infants identified prenatally required fewer transfers from birth hospital (p = 0.02). Additionally, those referred to MFM with craniofacial consultation had shorter lengths of stay when airway intervention was required (p = 0.05). CONCLUSION: Prenatal recognition of micrognathia may lead to early detection and management of RS. When RS is suspected, prenatal consultation with MFM and craniofacial team may further optimize care of the infant following delivery.

General Principles for Counseling and Management of Triplet Pregnancies.

Compared with singleton pregnancies, triplet pregnancies are associated with a significantly increased risk of adverse pregnancy outcomes. Early ultrasound examination is the best way to diagnose triplets, establish dating, and determine the number of placentas to provide appropriate counseling and monitoring. Dichorionic placentation adds risks specifically associated with a shared placenta, and limits options for intervention. Multifetal reduction is an option that can significantly improve pregnancy outcomes compared with non-reduced triplet pregnancies. Integration of a Maternal-Fetal Medicine specialist in the prenatal care for a triplet pregnancy reduces the risk of preeclampsia, preterm birth, low birthweight infants, perinatal mortality, and major neonatal morbidity.

Triplet pregnancy: What do we tell the prospective parents.

Experience managing triplet pregnancies has increased over the past few decades as the incidence has changed related to assisted reproductive practices. Physicians caring for women carrying triplets cannot predict an individual outcome or pregnancy course but must educate patients about the challenges related to these high risk pregnancies. Obstetric providers can describe the wide range of risks associated with triplet gestations, and the general plan for management, but ultimately parents must make decisions with potentially lifelong consequences. Here, we present the diagnostic criteria, common complications, and management options for triplet pregnancies, to help obstetricians counsel patients on the medical and psychosocial consequences of triplet pregnancy, potential complications, and multifetal reduction.

Mild fetal ventriculomegaly: diagnosis, evaluation, and management.

Ventriculomegaly is defined as dilation of the fetal cerebral ventricles and is a relatively common finding on prenatal ultrasound. The purpose of this document is to review the diagnosis, evaluation, and management of mild fetal ventriculomegaly. When enlargement of the lateral ventricles (≥10 mm) is identified, a thorough evaluation should be performed, including detailed sonographic evaluation of fetal anatomy, amniocentesis for karyotype and chromosomal microarray analysis, and a workup for fetal infection. In some cases, fetal magnetic resonance imaging may identify other central nervous system abnormalities and should be considered when this technology as well as expert interpretation is available. Follow-up ultrasound examination should be performed to assess for progression of the ventricular dilation. In the setting of isolated ventriculomegaly of 10-12 mm, the likelihood of survival with normal neurodevelopment is >90%. With moderate ventriculomegaly (13-15 mm), the likelihood of normal neurodevelopment is 75-93%. The following are Society for Maternal-Fetal Medicine recommendations: We suggest that ventriculomegaly be characterized as mild (10-12 mm), moderate (13-15 mm), or severe (>15 mm) for the purposes of patient counseling, given that the chance of an adverse outcome and potential for other abnormalities are higher when the ventricles measure 13-15 mm vs 10-12 mm (GRADE 2B); we recommend that diagnostic testing (amniocentesis) with chromosomal microarray analysis should be offered when ventriculomegaly is detected (GRADE 1B); we recommend testing for cytomegalovirus and toxoplasmosis when ventriculomegaly is detected, regardless of known exposure or symptoms (GRADE 1B); we suggest that magnetic resonance imaging be considered in cases of mild or moderate fetal ventriculomegaly when this modality and expert radiologic interpretation are available; magnetic resonance imaging is likely to be of less value if the patient has had a detailed ultrasound performed by an individual with specific experience and expertise in sonographic imaging of the fetal brain (GRADE 2B); we recommend that timing and mode of delivery be based on standard obstetric indications (GRADE 1C); we recommend that with isolated mild ventriculomegaly of 10-12 mm, after a complete evaluation, women be counseled that the outcome is favorable, and the infant is likely to be normal (GRADE 1B); we recommend that with isolated moderate ventriculomegaly of 13-15 mm, after a complete evaluation, women be counseled that the outcome is likely to be favorable but that there is an increased risk of neurodevelopmental disabilities (GRADE 1B).

Racial/ethnic standards for fetal growth: the NICHD Fetal Growth Studies.

OBJECTIVE: Fetal growth is associated with long-term health yet no appropriate standards exist for the early identification of undergrown or overgrown fetuses. We sought to develop contemporary fetal growth standards for 4 self-identified US racial/ethnic groups. STUDY DESIGN: We recruited for prospective follow-up 2334 healthy women with low-risk, singleton pregnancies from 12 community and perinatal centers from July 2009 through January 2013. The cohort comprised: 614 (26%) non-Hispanic whites, 611 (26%) non-Hispanic blacks, 649 (28%) Hispanics, and 460 (20%) Asians. Women were screened at 8w0d to 13w6d for maternal health status associated with presumably normal fetal growth (aged 18-40 years; body mass index 19.0-29.9 kg/m(2); healthy lifestyles and living conditions; low-risk medical and obstetrical history); 92% of recruited women completed the protocol. Women were randomized among 4 ultrasonography schedules for longitudinal fetal measurement using the Voluson E8 (GE Healthcare, Milwaukee, WI). In-person interviews and anthropometric assessments were conducted at each visit; medical records were abstracted. The fetuses of 1737 (74%) women continued to be low risk (uncomplicated pregnancy, absent anomalies) at birth, and their measurements were included in the standards. Racial/ethnic-specific fetal growth curves were estimated using linear mixed models with cubic splines. Estimated fetal weight (EFW) and biometric parameter percentiles (5th, 50th, 95th) were determined for each gestational week and comparisons made by race/ethnicity, with and without adjustment for maternal and sociodemographic factors. RESULTS: EFW differed significantly by race/ethnicity >20 weeks. Specifically at 39 weeks, the 5th, 50th, and 95th percentiles were 2790, 3505, and 4402 g for white; 2633, 3336, and 4226 g for Hispanic; 2621, 3270, and 4078 g for Asian; and 2622, 3260, and 4053 g for black women (adjusted global P < .001). For individual parameters, racial/ethnic differences by order of detection were: humerus and femur lengths (10 weeks), abdominal circumference (16 weeks), head circumference (21 weeks), and biparietal diameter (27 weeks). The study-derived standard based solely on the white group erroneously classifies as much as 15% of non-white fetuses as growth restricted (EFW <5th percentile). CONCLUSION: Significant differences in fetal growth were found among the 4 groups. Racial/ethnic-specific standards improve the precision in evaluating fetal growth.

Longitudinal Changes in Physical Activity during Pregnancy: National Institute of Child Health and Human Development Fetal Growth Studies.

INTRODUCTION: Exercise in pregnancy is associated with many perinatal benefits, but patterns of home, work, and commuting activity are not well described. We investigated longitudinal activity in singleton and twin pregnancy by activity domain and maternal characteristics. METHODS: In the National Institute of Child Health and Human Development Fetal Growth Studies cohorts, 2778 women with singleton and 169 women with twin gestations reported activity using the Pregnancy Physical Activity Questionnaire at up to six or seven study visits, respectively. Metabolic equivalent of task-hours per week (MET-h·wk -1 ) was calculated from reported activity. Baseline measurements (obtained between 10 and 13 wk) reflected past year activity. Linear mixed models estimated MET-h·wk -1 by domain (household/childcare, occupational, inactive, transportation, sports/exercise), self-reported race/ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, Asian/Pacific Islander), prepregnancy body mass index (<25, 25 to < 30, ≥30 kg·m -2 ), parity (0, ≥1), baseline activity (quartiles), and plurality (singleton, twin). RESULTS: Household/caregiving activity made up the largest fraction of reported MET-h·wk -1 at baseline (42%), followed by occupational activity (28%). Median summed activity declined 47%, from 297 to 157 MET-h·wk -1 , between 10 and 40 wk, largely driven by changes in household/caregiving (44% decline), and occupational activity (63% decline). Sports/exercise activity declined 55% but constituted only 5% of reported MET-h·wk -1 at baseline. At baseline, non-Hispanic Black women reported significantly higher activity than non-Hispanic White or Hispanic women, but differences did not persist across pregnancy. Across gestation nulliparous women reported significantly lower activity than parous women. Women with singleton gestations reported significantly more activity than women with twins from weeks 26 to 38. Baseline activity level was strongly associated with later activity levels. CONCLUSIONS: Measuring domains of activity beyond exercise, and collecting longitudinal measurements, is necessary to fully describe activity in diverse populations of pregnant women.

Nutrition during Pregnancy: Findings from the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singleton Cohort.

BACKGROUND: Accumulating evidence indicates that maternal diets are important for optimizing maternal and offspring health. Existing research lacks comprehensive profiles of maternal diets throughout pregnancy, especially in a racially/ethnically diverse obstetrical population. OBJECTIVE: The aim was to characterize diets in a longitudinal US pregnancy cohort by trimester, race/ethnicity, and prepregnancy BMI. METHODS: Data were obtained from pregnant women in the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singleton cohort (2009-2013). A food-frequency questionnaire (FFQ) at 8-13 wk of gestation assessed periconception and first-trimester diet (n = 1615). Automated, self-administered, 24-h dietary recalls targeted at 16-22, 24-29, 30-33, and 34-37 wk of gestation assessed second- and third-trimester diets (n = 1817 women/6791 recalls). The Healthy Eating Index-2010 (HEI-2010) assessed diet quality (i.e., adherence to US Dietary Guidelines). Variations in weighted energy-adjusted means for foods and nutrients were examined by trimester, self-identified race/ethnicity, and self-reported prepregnancy BMI. RESULTS: Mean (95% CI) HEI-2010 was 65.9 (64.9, 67.0) during periconception to the first trimester assessed with an FFQ and 51.6 (50.8, 52.4) and 51.5 (50.7, 52.3) during the second trimester and third trimester, respectively, assessed using 24-h recalls. No significant differences were observed between the second and third trimester in macronutrients, micronutrients, foods, or HEI-2010 components (P ≥ 0.05). Periconception to first-trimester HEI-2010 was highest among Asian/Pacific Islander [67.2 (65.9, 68.6)] and lowest among non-Hispanic Black [58.7 (57.5, 60.0)] women and highest among women with normal weight [67.2 (66.1, 68.4)] and lowest among women with obesity [63.5 (62.1, 64.9)]. Similar rankings were observed in the second/third trimesters. CONCLUSIONS: Most pregnant women in this cohort reported dietary intakes that, on average, did not meet US Dietary Guidelines for nonpregnant individuals. Also, diet differed across race/ethnic groups and by prepregnancy BMI, with the lowest overall dietary quality in all trimesters among non-Hispanic Black women and women with obesity. No meaningful changes in dietary intake were observed between the second and third trimesters.

Circulating cell-free DNA levels increase variably following chorionic villus sampling.

OBJECTIVE: Cell-free fetal DNA (cffDNA) in maternal plasma results from degradation of fetal and/or placental cells. Our objective was to determine if chorionic villus sampling (CVS) causes increased release of fetal and/or maternal DNA. METHODS: Fifty-two pregnant women were recruited prior to CVS, performed for clinical indications, at 10 5/7 to 13 2/7 weeks. Maternal blood was collected before and within 15 min after CVS. cffDNA was extracted from plasma. Real-time polymerase chain reaction (PCR) amplification of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the Y chromosome sequence DYS1 were used as measures of total and fetal DNA, respectively. All samples were analyzed in triplicate without knowledge of fetal gender. RESULTS: Sensitivity of DYS1 detection in male fetuses was 100% (n = 30); specificity in female fetuses was 100% (n = 22). While a majority of women had > 50% post-procedure increases in both fetal and total DNA, some showed post-procedure decreases. However, overall median proportional increases were not statistically significant. Gestational age (GA), placental location, and individual CVS operator did not correlate with changes in DNA levels. CONCLUSIONS: While there were no statistically significant overall changes in DNA levels after CVS, as-yet undiscovered variables may influence the extent of post-procedure release of cell-free DNA in the circulation of pregnant women.

The patient with asymptomatic shortened cervix at 23 to 28 weeks: is delivery imminent?

We investigated whether the presence of symptoms predicts the timing of subsequent spontaneous preterm birth in a cohort of women with cervical length (CL) <1.5 cm. A retrospective cohort study was conducted that included patients from 23 to 28 weeks' gestation with a CL <1.5 cm on routine ultrasound. Two groups were defined on the basis of presenting symptoms at the time of the ultrasound examination: asymptomatic patients and those with symptoms of preterm labor. The incidence of delivery within 2 weeks was determined for both groups. A total of 88 patients with CL <1.5 cm were identified from an ultrasound database. There were 52 patients with CL <1.5 cm and no symptoms. Of these, 1 (1.9%) delivered within 2 weeks. The remaining 36 patients had a CL <1.5 cm and symptoms of preterm labor. Of these, 11 (30.6%) delivered within 2 weeks (relative risk 15.9, 95% confidence interval 2.1 to 118). Premature cervical shortening at 23 to 28 weeks, in the absence of symptoms of preterm labor, is rarely associated with preterm delivery within 2 weeks. Following those patients clinically may prevent prolonged hospitalization and allow steroid administration closer to the date of delivery.

Preconceptional folate supplementation and the risk of spontaneous preterm birth: a cohort study.

BACKGROUND: Low plasma folate concentrations in pregnancy are associated with preterm birth. Here we show an association between preconceptional folate supplementation and the risk of spontaneous preterm birth. METHODS AND FINDINGS: In a cohort of 34,480 low-risk singleton pregnancies enrolled in a study of aneuploidy risk, preconceptional folate supplementation was prospectively recorded in the first trimester of pregnancy. Duration of pregnancy was estimated based on first trimester ultrasound examination. Natural length of pregnancy was defined as gestational age at delivery in pregnancies with no medical or obstetrical complications that may have constituted an indication for delivery. Spontaneous preterm birth was defined as duration of pregnancy between 20 and 37 wk without those complications. The association between preconceptional folate supplementation and the risk of spontaneous preterm birth was evaluated using survival analysis. Comparing to no supplementation, preconceptional folate supplementation for 1 y or longer was associated with a 70% decrease in the risk of spontaneous preterm delivery between 20 and 28 wk (41 [0.27%] versus 4 [0.04%] spontaneous preterm births, respectively; HR 0.22, 95% confidence interval [CI] 0.08-0.61, p = 0.004) and a 50% decrease in the risk of spontaneous preterm delivery between 28 and 32 wk (58 [0.38%] versus 12 [0.18%] preterm birth, respectively; HR 0.45, 95% CI 0.24-0.83, p = 0.010). Adjustment for maternal characteristics age, race, body mass index, education, marital status, smoking, parity, and history of prior preterm birth did not have a material effect on the association between folate supplementation for 1 y or longer and spontaneous preterm birth between 20 and 28, and 28 to 32 wk (adjusted HR 0.31, 95% CI 0.11-0.90, p = 0.031 and 0.53, 0.28-0.99, p = 0.046, respectively). Preconceptional folate supplementation was not significantly associated with the risk of spontaneous preterm birth beyond 32 wk. The association between shorter duration (<1 y) of preconceptional folate supplementation and the risk of spontaneous preterm birth was not significant after adjustment for maternal characteristics. However, the risk of spontaneous preterm birth decreased with the duration of preconceptional folate supplementation (test for trend of survivor functions, p = 0.01) and was the lowest in women who used folate supplementation for 1 y or longer. There was also no significant association with other complications of pregnancy studied after adjustment for maternal characteristics. CONCLUSIONS: Preconceptional folate supplementation is associated with a 50%-70% reduction in the incidence of early spontaneous preterm birth. The risk of early spontaneous preterm birth is inversely proportional to the duration of preconceptional folate supplementation. Preconceptional folate supplementation was specifically related to early spontaneous preterm birth and not associated with other complications of pregnancy.

Use of array comparative genomic hybridization for prenatal diagnosis of fetuses with sonographic anomalies and normal metaphase karyotype.

OBJECTIVE: To prospectively study the addition of array comparative genomic hybridization (CGH) to the prenatal evaluation of fetal structural anomalies. METHODS: Pregnant women carrying fetuses with a major structural abnormality were recruited at the time of invasive procedure for chromosome analysis. Only women whose fetuses had a normal karyotype (n = 50) were subsequently evaluated by array CGH using one of two arrays (1887 clones covering 622 loci or subsequently 4685 clones covering 1500 loci). RESULTS: The mean gestational age of the fetuses was 24.5 weeks (range 11-38 weeks). The most prevalent anomalies were cardiac, central nervous system, skeletal, and urogenital. The median turnaround time for culturing and array CGH diagnosis was 18 days (range 2-72). Four of 50 fetuses had abnormal array results. One (2%) was clinically significant and three (6%) were inherited or benign variants. CONCLUSIONS: Array CGH studies in fetuses with sonographic anomalies and normal metaphase karyotype detected clinically significant copy number alterations in 1 of 50 cases. This percentage (2%) is consistent with prior prenatal reports. Further studies are warranted to more precisely identify which fetal anomalies are associated with copy number alterations of clinical significance.