, tests, or 2 MD x ClinicalTrials.gov, & GYNECOLOGY , Sean C. Blackwell, PhD Among uncomplicated tests were used to assess group differences. t From July 11, 2016, to May 24, 2017, 852 0.05; loss to follow-up 5%). All women were included 5 needed to have 80%primary power composite to outcome detect from an 10%in increase in the control in intervention to the group 25% (baselinea rate 10%; two-tailed; in the intent-to-treat analysis. Fisher exact, (Obstet Gynecol 2018;132:1358–67) DOI: 10.1097/AOG.0000000000002970 although we were underpowered forCLINICAL these endpoints. NCT02702999. TRIAL REGISTRATION: RESULTS: women wererandomized screened as for follows: 102serial eligibility in ultrasound and routine examinations. carecomparable 206 in The and baseline characteristics. 104 two were The primary in posite groups com- outcome were was significantlywho higher were in among the women ultrasoundroutine examination care group group (27% than vs the 1.64–7.17); 8%; five relative risk women 3.43, 95% (95%identify CI at CI least 3–11) one weremalities. of Although we needed the were composite underpowered to to ultrasound detect a abnor- nificant sig- difference, theoccurred with following similar frequency secondary innation the endpoints ultrasound group exami- than thesulting routine care from group: abnormal induction(14% ultrasound re- vs examination 6%), findings cesareanprespecified delivery in composite labor maternal (5% morbiditygroups) vs (9% and 6%), in composite and neonatal both morbidity (1%CONCLUSION: vs 4%). between 24 0/7third-trimester and 30 ultrasound 6/7cantly examinations weeks more were ofgrowth likely gestation, signifi- or serial to amnioticheight fluid identify and than indicated abnormalities measurements ultrasoundences examination. of of in No fundal differ- maternal fetal and neonatal outcomes were noted, two-sample HonDSc , Claudia Pedroza, , MD MD s requirements for ’ he American College of Obstetricians t by , Baha M. Sibai, ª MD Original Research Copyright Unauthorized reproduction of this article is prohibited. To evaluate whether serial ultrasound ex- Women without complications between 24 and Gynecologists. Published by Wolters Kluwer Health, Inc. February 3, 2018, Dallas, Texas. –

VOL. 132, NO. 6, DECEMBER 2018 s Health Research. ’

Tyisha L. Barrett, and Suneet P. Chauhan, 1358 The authors did not report any© potential 2018 conflicts by of theby interest. American Wolters College Kluwer of Health, ObstetriciansISSN: Inc. and 0029-7844/18 All Gynecologists. rights Published reserved. Gynecology, and ReproductiveCenter at Sciences, Houston, Universityemail: 6431 [email protected]. of Fannin Texas Street, Health MSBFinancial 3.270 Science Disclosure Houston, TX 77030; Received June 7,August 2018. 23, 2018. Received Peer in reviewB189. history revised is available form at http://links.lww.com/AOG/ August 10,Corresponding 2018. author: Accepted Olaide Ashimi Balogun, MD, Department of Obstetrics, January 29 Each author has indicatedauthorship. that he or she has met the journal Center at Houston, Houston, Texas. Supported in partWomen by the LarryPresented C. at the Gilstrap 37th annual MD meeting of Center the Society for for Perinatal Maternal-Fetal Medicine, and From the DepartmentMcGovern Medical of School, Obstetrics, andBased the Gynecology, Medicine, Center Department and for of Clinical Reproductive Research Pediatrics, and Sciences, University Evidence- of Texas Health Science . Theence secondary outcome of wasamong the composite the pres- two maternal groups. A or total neonatal of 206 morbidity participants was arm). The primary outcomemalities was of fluid a volume composite andpolyhydramnios; of growth: abnor- fetal or growth restriction; or large for 0/7 and 30(NCT0270299) 6/7 to weeks eitherultrasound of routine examination gestation care were every (control randomized arm) 4 or weeks (intervention that are uncomplicated between 24 0/7of and gestation. 30 6/7 weeks METHODS: OBJECTIVE: aminations in the thirdof a trimester composite increase of growth identification when or amniotic compared fluid with abnormalities routine care among pregnancies A Randomized Controlled Trial Olaide Ashimi Balogun, Uncomplicated Pregnancies Serial Third-Trimester Ultrasonography Compared With Routine Care in Ultrasonography:

Downloaded from https://journals.lww.com/greenjournal by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3TDbD+Y6NAIH9mhZe+OAo47wPbjrTWLsWPNit4YQiE6KcLXJXE7nthw== on 12/03/2018 Downloaded from https://journals.lww.com/greenjournal by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3TDbD+Y6NAIH9mhZe+OAo47wPbjrTWLsWPNit4YQiE6KcLXJXE7nthw== on 12/03/2018 urrently, the American College of Obstetricians a singleton with no major prenatally Cand Gynecologists (ACOG) recommends that diagnosed fetal anomalies, and who had an estimated the first step in screening for abnormalities of fetal due date based on in vitro fertilization or ultrasound growth or volume in uncomplicated examination before 22 0/7 weeks.18 Women were pregnancies is serial measurements of fundal height, excluded for any medical complication or co- starting at 24 weeks of gestation. If a discrepancy morbidity at the time of randomization (Box 1). If between gestational age and measurement of the fun- a complication developed after randomization, dus is present, the second step is to obtain an ultra- women remained in the group to which they were sound examination to assess fetal weight and amniotic randomized. fluid volume.1,2 As a result of routine care, a substan- Trained research staff approached eligible women tial portion of small for gestational age ( and obtained informed, written consent between 24 less than the 10th percentile for gestational age) or large for gestational age (LGA; birth weight greater than the 90th percentile for gestational age) and oli- Box 1. Exclusion Criteria gohydramnios or is unidentified3–6 First ultrasound examination after 22 wk of gestation and therefore may not benefit from antepartum sur- Women with any of the following comorbidities: veillance and interventions.7–9 a. Autoimmune disorders (antiphospholipid anti- Abnormal growth occurs in 16% of uncompli- body, systemic lupus erythematous, rheuma- cated pregnancies.10 These pregnancies are more toid arthritis, scleroderma) b. Cerclage in the index pregnancy likely to result in stillbirths or have neonates with c. Diabetes mellitus—gestational or pregestational 11–13 morbidities. Abnormalities of amniotic fluid vol- d. Hematologic disorders (coagulation defects, ume—oligohydramnios or polyhydramnios—occur in sickle cell disease, thrombocytopenia, and up to 10% of low-risk pregnancies and are associated known thrombophilia) with stillbirth, low Apgar score, and neonatal mortal- e. Hypertension (chronic or gestational hyperten- 6,14–17 sion, or preeclampsia with or without severe ity. There is an impetus to improve the identi- features before enrollment) fication of fetal growth restriction (estimated fetal f. Human immunodeficiency virus weight less than the 10th percentile for gestational g. Prior obstetric history of 1) small for gesta- age), ultrasonographic LGA (estimated fetal weight tional age; 2) before 34 wk of greater than the 90th percentile for gestational age), gestation; 3) severe preeclampsia, eclampsia, hemolysis, elevated liver enzymes, and low oligohydramnios, and polyhydramnios. platelet count syndrome; and 4) stillbirth after The purpose of this randomized clinical trial was 24 wk of gestation or neonatal death to compare the identification of composite of abnor- h. Preterm labor or ruptured membranes before malities of fluid volume and growth—oligohydram- enrollment nios, polyhydramnios, fetal growth restriction, or i. Psychiatric disorder (bipolar, depression) on — medication ultrasonographic LGA in uncomplicated pregnancies j. previa or 3rd-trimester bleeding by performing serial fundal height measurements and k. Renal insufficiency (serum creatinine greater ultrasound examination if there was a discrepancy than 1.5 mg/dL) compared with serial ultrasound examination every l. Chronic lung disease (asthma requiring medi- 4 weeks, regardless of the measurement of fundal cation, chronic obstructive pulmonary disease) m. Fetal red blood cell isoimmunization height. We focused on this composite because after n. Seizure disorder on medication a normal second-trimester anatomy ultrasound exam- o. Thyroid disease on medication ination, these are the most common abnormalities p. Body mass index greater than 40 kg/m2 at first identified6 and because the purpose of fundal height prenatal visit measurements is to screen for these four abnormal Major fetal anomaly including: conditions. a. Anencephaly b. Spina bifida MATERIALS AND METHODS c. Bilateral renal agenesis d. Cystic hygroma with hydrops This single-centered randomized controlled trial com- e. Diaphragmatic hernia menced after obtaining approval from institutional f. Congenital heart defects – review board at The McGovern Medical School Women who were unable to sign a consent in the University of Texas at Houston and registering on English language ClinicalTrials.gov (NCT0270299). Inclusion criteria Institutionalized individuals (prisoners) were women who were at least 18 years old, had

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Copyright ª by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. 0/7 to 30 6/7 weeks of gestation after it was pocket. Oligohydramnios was defined as amniotic determined they did not have .19 fluidindex5.0cmorlessormaximumvertical Enrolled participants were randomly assigned in pocket 2.0 cm or less. Polyhydramnios was defined a one-to-one ratio using permuted block randomiza- as an amniotic fluid index 24.0 or greater or maxi- tion to prevent imbalances between groups. The ran- mum vertical pocket 8.0 cm or greater.2 All ultra- dom allocation sequence was developed in R software sound reports were made available to the treating by the statistician (C.P.) who was not involved in the health care providers. Decision-making regarding conduct of the study. The randomization table was the management of each pregnancy was at the discre- uploaded to REDCap. Treatment allocation was as- tion of the individual clinician. The nomogram pub- signed through the randomization module. Partici- lished by Alexander et al23 was used to categorize pants were assigned to either routine care, which newborns as small for gestational age (birth weight included serial fundal height measurements at each less than the 10th percentile for gestational age) or clinical appointment prompting an ultrasound exam- as actual LGA (birth weight greater than the 90th ination if a discrepancy was present (routine arm), or percentile for gestational age). ultrasound examination every 4 weeks (at approxi- Women recruited to the study were followed mately 30, 34, and 38 weeks of gestation), regardless through delivery and information about the remain- of fundal height measurements (intervention arm). der of their antepartum care; intrapartum and neo- Women enrolled, ultrasonographers, and maternal– natal outcomes were abstracted. To keep abstracted fetal medicine attendings reviewing the ultrasound data consistent, one author (O.A.B.) reviewed all the examinations and the chart abstractor were not blin- charts and was aware of the group allocation. Com- ded to the group allocation. posite maternal morbidity for this trial was defined as Clinicians treating these women were informed of any of the following: 1) chorioamnionitis, 2) cesarean the ultrasound findings if any of the following were delivery in labor, 3) wound infection, 4) transfusion, 5) noted: fetal growth restriction, LGA, oligohydram- deep venous thrombus or pulmonary embolism, 6) nios, polyhydramnios, or any ultrasound findings that admission to the intensive care unit, or 7) death. would influence clinical treatment (eg, spontaneous Composite neonatal morbidity was defined as any of bradycardia or previously undetected fetal anomaly). the following: 1) Apgar score less than 5 at 5 minutes, Women with abnormal findings were notified. The 2) umbilical arterial pH less than 7.00, 3) intraven- clinicians treated their patients according to ACOG tricular hemorrhage grade III or IV, 4) periventricular guidelines.1,7,8 In both groups, additional ultrasound leukomalacia, 5) intubation for longer than 24 hours, examinations could be obtained if deemed necessary 6) necrotizing enterocolitis grade 2 or 3, 7) stillbirth by the obstetric care provider if complications devel- after randomization, or 8) neonatal death (within 28 oped (eg, preterm labor, decreased fetal movements, days) of birth in the index pregnancy. or development of hypertensive disease). Registered With routine care, among uncomplicated preg- diagnostic medical ultrasonographers did all the ultra- nancies, the identification of the composite of abnor- sound examinations and a maternal–fetal medicine malities of fluid volume and growth abnormalities is subspecialist reviewed all ultrasound examinations. 10%.6 To increase the detection of the composite of Obstetrics–gynecology faculty and residents training abnormalities of fluid volume and growth abnormal- under their supervision did all of the fundal height ities from 10% in the control arm to 25% in the inter- measurements. To reflect daily clinical practice, vention arm, a total of 194 women needed to be standardization of measurements of biometric parts, randomized (a55%; power580%). We estimated that amniotic fluid, or fundal height was not done for this 5% of women would be lost to follow-up based on trial. a previous pilot study.6 Thus, the total sample size The fetal weight was estimated by obtaining for the trial was 206 women. measurements of the biparietal diameter, head cir- Descriptive statistics were used to summarize all cumference, abdominal circumference, and femoral study variables. Categorical variables were reported diaphysis length. The regression equation proposed as frequencies and percentages. Fisher exact, x2 tests, by Hadlock et al20 wasusedtoestimatethefetal or two-sample t tests were used to assess group differ- weight. Fetal growth abnormalities were defined if ences (routine vs serial ultrasound examinations) in the estimated fetal weight was less than the 10th per- patient outcomes. Subgroup analysis was performed centile or greater than the 90th percentile for gesta- using similar methods. Relative risk (RR) and 95% CI tional age.1,21,22 Amniotic fluid was assessed using were calculated as was number needed to identify either the amniotic fluid index or maximum vertical the primary composite outcome. All analyses were

1360 Ashimi Balogun et al Third-Trimester Ultrasonography vs Routine Care OBSTETRICS & GYNECOLOGY

Copyright ª by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. conducted using Stata 13.0. All randomized women their third trimester of pregnancy. The most common were included in the intent-to-treat analysis. antepartum complication was gestational hyperten- sion or preeclampsia (Table 3). RESULTS The primary composite outcome was more fre- Recruitment began July 11, 2016, and concluded May quently identified among women who had serial 24, 2017. Of the 852 women screened for eligibility, ultrasound examinations than those who received 626 patients did not meet inclusion criteria. The most routine care (27% vs 8%; RR 3.4, 95% CI 1.6–7.2). common reason for exclusion was women with The number needed to treat was five women (95% CI comorbidities such as pregestational or gestational 3–11). Although the study was not powered to detect diabetes or chronic hypertension. Two hundred differences in the individual components of the com- twenty-six women were approached to participate in posite outcome, there was a difference in identifica- the study and 20 declined. The remaining 206 women tion of polyhydramnios between the serial ultrasound were consented and 102 were randomized to receive examination and routine care groups (11% vs 2%; RR routine care and 104 to receive serial ultrasound 5.4, 95% CI 1.2–23.7). No significant difference in the examinations (Fig. 1). One woman in the routine care detection of fetal growth restriction, LGA, or oligohy- group delivered at an outside hospital and the out- comes of delivery were unavailable for analysis. dramnios was noted (Table 4). The two groups were comparable in baseline Analysis limited to women who did not develop characteristics (Table 1). Women recruited in the trial any complications after randomization (eg, preterm were ethnically diverse, approximately 4 in 10 were labor or hypertensive disease) also indicated the nulliparous, and approximately 70% had body mass primary composite outcome was significantly more indexes (calculated as weight (kg)/[height (m)]2) less frequent among women who had serial ultrasound than 30 at the first prenatal visit. The total number of examinations than routine care (27% vs 8%; RR 3.7, ultrasound examinations was higher in the interven- 95% CI 1.5–9.4). The detection of polyhydramnios tion arm than the control arm. The indications for the differed between the two groups but the 95% CI was ultrasound examinations differed as did the gesta- wide as a result of the sample size (Table 5). The tional age at delivery (P,.01; Table 2). The total num- number needed to treat was also five women (95% ber of antepartum complications after randomization CI 3–13). was similar in the two groups with approximately one Prespecified composite maternal morbidity was in four low-risk women developing a complication in similar in both groups (9% in both serial ultrasound

Figure 1. Flow diagram. *Comorbidity such as hypertension or diabetes. Ashimi Balogun. Third-Trimester Ultraso- nography vs Routine Care. Obstet Gynecol 2018.

VOL. 132, NO. 6, DECEMBER 2018 Ashimi Balogun et al Third-Trimester Ultrasonography vs Routine Care 1361

Copyright ª by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. Table 1. Characteristics of Participants at Randomization

Characteristic Routine Care (n5102) Serial 3rd-Trimester USE (n5104)

Maternal age (y) 18–19 5 (5) 10 (10) 35 or older 10 (10) 12 (12) Race–ethnicity Black 32 (31) 34 (33) White 23 (23) 25 (24) Hispanic 20 (20) 22 (21) Other 27 (27) 23 (22) Nulliparity 43 (42) 39 (38) Insurance Medicaid 66 (65) 69 (66) Private 36 (36) 35 (34) BMI at 1st prenatal visit (kg/m2)* Less than 30 74 (73) 77 (74) 30.0–39.9 28 (27) 27 (26) 1st ultrasound examination (wk) 12.964.3 12.964.3 Gestational age at randomization (wk) 29.261.0 29.061.1 USE, ultrasound examination; BMI, body mass index. Data are n (%) or mean6SD. * Women with BMIs of 40 or higher were excluded. examinations compared with routine care group; RR care group; RR 0.2, 95% CI 0.03–2.1), but we were 1.0, 95% CI 0.4–2.3), but we were not powered to underpowered to detect a difference (Table 6). detect a difference. There were no episodes of deep The gestational age epoch (less than 32 0/7, 32 0/ venous thrombus or pulmonary embolism, admission 7–34 6/7, 35 0/7–36 6/7, or at least 37 0/7 weeks of to the intensive care unit, or maternal deaths in either gestation) when the abnormal condition was initially groups. The prespecified composite neonatal morbid- identified differed between the groups (P5.02). The ity was also similar in both groups (1% in the serial rate of having a or umbilical artery ultrasound examination group vs 4% in the routine Doppler, because of the abnormality noted on

Table 2. Ultrasound Examinations—Indications and Gestational Age

Routine Care (n5101) Serial 3rd-Trimester USE (n5104) P/RR (95% CI)

USE for fetal growth 58 279 4.6 (3.5–6.1) USE per protocol 0 (0) 264 (2.54) — No. of women who received additional USE 39 10 .2 (0.1–0.5) Indications for additional USE Bleeding 1 (0.026) 0 (0) — Decreased fetal movement 1 (0.026) 3 (0.3) 11.7 (1.2–112.5) GA and FH disparity 43 (1.1) 6 (0.6) .5 (0.2–1.3) HTN disease of pregnancy* 4 (0.10) 1 (0.1) 1.0 (0.1–8.7) Preterm labor 0 (0) 0 (0) — PROM 0 (0) 0 (0) — Others† 9 (0.23) 7 (0.7) 3.0 (1.1–8.1) GA when USE was done (wk) Less than 32 0/7 3 (5) 93 (33) ,.01 32 0/7–34 6/7 23 (40) 95 (34) 35 0/7–36 6/7 19 (33) 19 (7) 37 0/7 or greater 13 (22) 72 (26) USE, ultrasound examination; RR, relative risk; GA, gestational age; FH, fundal height; HTN, hypertensive; PROM, premature . Data are n (number of USE per woman) for USE per protocol and additional USE per indications and n (%) for GA when USE was done. * Includes and preeclampsia with or without severe features. † Includes cholestasis, fall, fetal ventricular tachycardia.

1362 Ashimi Balogun et al Third-Trimester Ultrasonography vs Routine Care OBSTETRICS & GYNECOLOGY

Copyright ª by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. Table 3. Antepartum Complications After Randomization

Routine Care (n5102) Serial 3rd-Trimester USE (n5104) RR (95% CI)

Antepartum complications—total* 32 (31) 29 (28) 0.9 (0.6–1.4) GHTN or preeclampsia 15 (15) 21 (20) 1.4 (0.8–2.5) Decreased fetal movement 4 (4) 3 (3) 0.7 (0.2–3.2) Preterm labor 5 (5) 3 (3) 0.6 (0.1–2.4) PROM at less than 37 wk of gestation 1 (1) 3 (3) 2.9 (0.3–27.8) Others† 9 (9) 2 (2) 0.2 (0.05–0.98) USE, ultrasound examination; RR, relative risk; GHTN, gestational hypertension; PROM, premature rupture of membranes. Data are n (%) unless otherwise specified. * Defined as admission for at least 24 hours for one of the antepartum complications. † Others includes cholestasis, pyelonephritis, fall, fetal ventricular tachycardia. ultrasound examination (ie, polyhydramnios or intra- tational age at delivery, the rate of induction, and of uterine growth restriction), was similar between the cesarean delivery. two groups (Table 7). Estimates indicate that upward of two thirds of Gestational age at delivery was comparable in the pregnancies are low risk.6,24,25 Although there are two groups with only 9% of women delivering before multiple potential etiologies of adverse outcomes in 37 weeks of gestation in both groups. The most low-risk pregnancies, the most common ones that common reason for induction of labor before 37 are amenable to interventions are aberrations of fetal weeks of gestation was preeclampsia with severe growth or of amniotic fluid.6,10–17 Small-for- features. There was no difference in delivery route gestational-age and LGA newborns are significantly between the two groups (RR 0.8, 95% CI 0.5–1.2). more likely to be stillborn and have neonatal morbid- The most common reason for cesarean delivery in ities.1,11,21 Furthermore, pregnancies complicated both groups was for women who declined a trial of with oligohydramnios or polyhydramnios are associ- labor and desired a repeat cesarean delivery (Table 8). ated with stillbirth, low Apgar score, and neonatal mortality.14–17 Therefore, even among uncomplicated DISCUSSION pregnancies, identification of abnormalities in fetal Our randomized trial suggests that among women growth or in amniotic fluid is central to antepartum with uncomplicated pregnancies at 24 0/7 to 30 6/7 care because the combination of surveillance and in- weeks of gestation, serial third-trimester ultrasound terventions could mitigate adverse outcomes.1,7,8,21 examinations are more likely to identify a composite Our randomized trial differs from others on the of abnormalities of fetal growth or amniotic fluid than topic26–30 vis-à-vis the enrollment criteria, the fre- routine care. The number of women who need serial quency of the ultrasound examinations in the inter- ultrasound examinations in the third trimester to vention group, and the primary outcome being identify an abnormal condition is five (95% CI a composite of abnormalities of growth or amniotic 3–11). Although the trial is underpowered for assess- fluid. Prior randomized trials on ultrasound examina- ment of peripartum outcomes, the maternal and tion after 24 weeks of gestation focused on either neonatal adverse outcomes were similar as were ges- growth restriction26,28–30 or placental grading,27

Table 4. Primary Outcome

Routine Care (n5102) Serial 3rd-Trimester USE (n5104) RR (95% CI)

Primary composite outcome* 8 (8) 28 (27) 3.4 (1.6–7.2) FGR 2 (2) 8 (8) 3.9 (0.9–18.0) Ultrasonographic LGA 2 (2) 8 (8) 3.9 (0.9–18.0) Oligohydramnios 2 (2) 4 (4) 1.9 (0.4–10.5) Polyhydramnios 2 (2) 11 (11) 5.4 (1.2–23.7) USE, ultrasound examination; RR, relative risk; FGR, fetal growth restriction (estimated fetal weight less than the 10th percentile for gestational age—during any ultrasound examination); LGA, large for gestational age (estimated fetal weight greater than the 90th percentile for gestational age—during any ultrasound examination). Data are n (%) unless otherwise specified. * The trial was not powered to detect a difference in the four components of the primary composite outcome.

VOL. 132, NO. 6, DECEMBER 2018 Ashimi Balogun et al Third-Trimester Ultrasonography vs Routine Care 1363

Copyright ª by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. Table 5. Primary Outcome Without Antepartum Complications

Routine Care Serial 3rd-Trimester USE (n5102) (n5104) RR (95% CI)

Women without antepartum complication after 70 (69) 75 (72) 1.1 (0.9–1.3) randomization Women with primary outcome without antepartum 5 (7) 20 (27) 3.7 (1.5–9.4) complications FGR 1 (1) 5 (7) 4.7 (0.6–39.0) Ultrasonographic LGA 1 (1) 6 (8) 5.6 (0.7–45.4) Oligohydramnios 2 (2) 2 (3) 0.9 (0.1–6.4) Polyhydramnios 1 (1) 9 (12) 8.4 (1.1–64.6) USE, ultrasound examination; RR, relative risk; FGR, fetal growth restriction (estimated fetal weight less than the 10th percentile for gestational age—during any ultrasound examination); LGA, large for gestational age (estimated fetal weight greater than the 90th percentile for gestational age—during any ultrasound examination). Data are n (%) unless otherwise specified. whereas we focused on a composite of abnormal con- fluid predominates. It is also noteworthy to mention ditions and did not assess placental grade. With that most of the prior randomized trials on the topic hypertensive disease of pregnancy, the is primar- were done in the 1980s to 1990s26–28 or ily at risk for growth restriction and oligohydramnios, abroad26,27,29,30 and do not reflect contemporary whereas in diabetes, the risks are primarily those of practice in the United States. macrosomia and polyhydramnios.26,28–30 Among The limitations of this randomized trial should be uncomplicated pregnancies, however, it is uncertain acknowledged. The likelihood of identifying individ- which aspect of abnormality in growth or amniotic ual component of the composite primary outcome of

Table 6. Composite Maternal and Neonatal Morbidity

Routine Care (n5101)* Serial 3rd-Trimester USE (n5104) RR (95% CI)

Composite maternal morbidity 9 (9) 9 (9) 1.0 (0.4–2.3) Chorioamnionitis 4 (4) 5 (5) Cesarean delivery in labor 6 (6) 5 (5) Postpartum hemorrhage 3 (3) 2 (2) Transfusion 3 (3) 1 (1) Wound infection 0 (0) 1 (1) — DVT or PE 0 (0) 0 (0) — Admission to ICU 0 (0) 0 (0) — Death 0 (0) 0 (0) — Composite neonatal morbidity 4 (4) 1 (1) 0.2 (0.03–2.1) Apgar score less than 5 at 5 min 1 (1) 0 (0) — Umbilical arterial pH less than 7.00† 2 (2) (n592) 0 (0) (n589) — Intubation longer than 24 h 1 (1) 1 (1) Periventricular leukomalacia 0 (0) 0 (0) — IVH grade III or IV 1 (1) 0 (0) — NEC grade II or III 0 (0) 0 (0) — Stillbirth 0 (0) 0 (0) — Neonatal death (within 28 d) 1 (1) 0 (0) — Birth weight SGA 8 (8) 8 (8) 1.0 (0.4–2.5) LGA 7 (7) 3 (3) 0.4 (0.1–1.6) USE, ultrasound examination; RR, relative risk; DVT, deep venous thrombus; PE, pulmonary embolism; ICU, intensive care unit; IVH, intraventricular hemorrhage; NEC, necrotizing enterocolitis; SGA, small for gestational age (birth weight less than the 10th percentile for gestational age using nomogram by Alexander et al); LGA, large for gestational age (birth weight greater than the 90th percentile for gestational age using nomogram by Alexander et al). Data are n (%) unless otherwise specified. * One patient delivered at an outside hospital and the data were not available. † Umbilical artery acid base was assessed in 92 (N) cases of routine care and in 89 (N) cases in the serial 3rd-trimester USE.

1364 Ashimi Balogun et al Third-Trimester Ultrasonography vs Routine Care OBSTETRICS & GYNECOLOGY

Copyright ª by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. Table 7. Ultrasound Findings Among Women With Primary Outcomes

Routine Care (n58) Serial 3rd-Trimester USE (n528) P/RR (95% CI)

Initial detection of USE abnormality* (wk of gestation) Less than 32 0/7 2 (25) 10 (36) .02 32 0/7–34 6/7 2 (25) 8 (29) 35 0/7–36 6/7 3 (38) 0 (0) 37 0/7 or greater 1 (13) 10 (36) Resolution of abnormal USE findings* 2 (25) 9 (32) 1.3 (0.3–4.8) Biophysical profile performed for Abnormalities noted on USE 5 (63) 21 (75) 1.2 (0.7–2.1) Obstetric complications† 1 (13) 1 (4) .3 (0.02–4.1) UA Doppler for FGR 2 (25) 8 (29) 1.1 (0.3–4.3) USE, ultrasound examination; RR, relative risk; UA, umbilical artery; FGR, fetal growth restriction (ultrasound estimated fetal weight less than the 10th percentile for gestational age). Data are n (%) unless otherwise specified. * Sonographic estimate fetal weight less than the 10th percentile or greater than the 90th percentile for gestational age; oligo- or polyhydramnios. † Bleeding, decreased fetal movement, hypertensive disease of pregnancy; preterm labor; premature rupture of membranes, others. fetal growth abnormalities or oligohydramnios was of the ultrasound examinations were done by regis- similar in both groups, perhaps as a result of the tered diagnostic medical ultrasonography-certified ul- sample size. Nonetheless, the trend was toward trasonographers; hence, our findings may not be improved identification of abnormal growth with applicable to women who have third-trimester ultra- serial ultrasound examinations. Previous reports, sound examinations by clinicians during prenatal vis- however, have described the accuracy of identifying its.31 The study was done at a tertiary, urban teaching fetal growth restriction and LGA with ultrasound center, where the population and clinical practice dif- examinations.1,2,6,9,22,29,30 This single-center trial was fer from other locations. We acknowledge that not powered to detect differences in any obstetric or another limitation of this randomized trial is that the neonatal outcomes. Considering the infrequent rate of participants and clinicians were not blinded to group morbidity with uncomplicated pregnancies,10,12,13 allocation. This shortcoming, however, permits us a large multicenter randomized trial is required to to ascertain the changes in clinical practices demonstrate improvement, if any, in outcomes. All and outcomes if the clinical practice of routine

Table 8. Intrapartum Outcomes

Routine Care (n5101)* Serial 3rd-Trimester USE (n5104) P/RR (95% CI)

Gestational age at delivery (wk) Less than 37 0/7† 9 (9) 9 (9) .90 37 0/7–38 6/7 31 (31) 35 (34) 39 0/7 or greater 61 (60) 60 (58) Induction 42 (42) 31 (30) .7 (0.5–1.0) Induction for ultrasound abnormality alone 6 (6) 15 (14) 2.43 (0.98–6.01) Delivery route .8 (0.5–1.2) Vaginal 73 (72) 81 (79) Cesarean 28 (28) 22 (21) Cephalopelvic disproportion 2 (7) 3 (14) 1.9 (0.3–10.4) NR-FHR 9 (32) 5 (23) .7 (0.3–1.8) Repeat 14 (50) 10 (54) .9 (0.5–1.6) Other‡ 3 (11) 2 (9) .8 (0.2–4.6) USE, ultrasound examination; RR, relative risk; NR-FHR, nonreassuring fetal heart rate tracing. Data are n (%) unless otherwise specified. * One patient delivered at an outside hospital and the peripartum data were unavailable for analysis. † The most common reason for preterm induction was preeclampsia with severe features (4% in routine care and 6% in serial 3rd-trimester USE). ‡ Other includes cesarean delivery as a result of herpes simplex virus lesion at the time of delivery, malpresentation, inability to abduct as a result of hip fracture.

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