Maternal Serum Α-fetoprotein Research Articles

Elevation of Maternal Serum α-Fetoprotein: Implications for the Neonate.

Elevation of Maternal Serum α-Fetoprotein: Implications for the Neonate.

Combined maternal risk factors and the Quadruple test to predict late-onset preeclampsia in pregnant Thai women

BackgroundThis study aimed to evaluate the predictive power of a model combining maternal risk factors and the Quadruple screen test for late-onset preeclampsia (PE).MethodsAll pregnant women that received the Quadruple test for Down syndrome at 15+ 0-20+ 6 weeks’ gestation were recruited. Maternal serum α-fetoprotein, β-human chorionic gonadotropin, unconjugated estriol, and inhibin A were measured as multiples of the median. A logistic regression model was used to identify predictors associated with late-onset PE with severe features. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to assess the model’s predictive ability.ResultsFifty-five of the 2,000 pregnant women had PE, and 31 of 55 women had late-onset PE. Multivariate analysis identified maternal age ≥ 35 years, inhibin A, history of previous PE, history of infertile, cardiac disease, chronic hypertension, and thyroid disease as significant risk factors. The area under the curve of the receiver operating characteristic curve was 0.78. The likelihood ratio to predict late-onset PE was 49.4 (total score > 60).ConclusionsOur model combining serum inhibin A with maternal risk factors was useful in predicting late-onset PE. Close monitoring of these patients is recommended.

Maternal Serum α-Fetoprotein Levels during Pregnancy and Testicular Cancer in Male Offspring: A Cohort Study within a Danish Pregnancy Screening Registry.

Testicular cancer is believed to originate from disruptions of normal androgen-estrogen balance in-utero. α-fetoprotein (AFP) may modify fetal response to estrogens via estrogen interaction. In a cohort study, we investigated the association between circulating maternal pregnancy AFP and testicular cancer risk in offspring. Of the 56,709 live-born males from a pregnancy screening registry in 1980-1995, our study included 50,519 singleton males with available second trimester blood samples from their mothers and complete covariate ascertainment. Testicular cancer diagnoses and covariate data were obtained from nationwide Danish health registries. Cox regression and Kaplan-Meier analyses estimated the prospective risk of testicular cancer (all, seminoma, nonseminoma) by AFP multiples of the median. During follow-up, 163 (0.3%) of the included males developed testicular cancer, of which 89 (54.6%) were nonseminomas. Maternal serum AFP levels greater than/equal to the median were associated with a relative risk of testicular cancer close to unity (RR 1.04, 95% CI 0.76; 1.41) compared to AFP below the median. Associations differed by type of testicular cancer (RRseminoma 0.81, 95% CI 0.51; 1.29, RRnonseminoma 1.31, 95% CI 0.85; 2.02). On balance, our findings do not support that serum AFP in pregnancy can be used as a predictor of testicular cancer in offspring.

The diagnostic accuracy of maternal serum alpha-fetoprotein variants (AFP-L2 and AFP-L3) in predicting fetal open neural tube defects and abdominal wall defects

IntroductionTo evaluate a risk model of the maternal serum α-fetoprotein variants L2 and L3 (AFP-L2 and AFP-L3) for predicting fetal open neural tube defects (ONTD) and abdominal wall defects (AWD). MethodsSubjects were divided into the ONTD group (21), the AWD group (16) and the control group (38). Comparative analysis was performed using a risk model, receiver operating characteristic (ROC) curves and area under the curve (AUC) were used for screening performance of AFP-L2 and AFP-L3. ResultsAFP-L2 and AFP-L3 concentrations in the ONTD group and the AWD group were both significantly higher than those in the control group (P < 0.001). The AUC for screening ONTD or AWD using AFP-L2 was 0.830 [95% confidence interval (CI):0.734–0.926, P < 0.001], while using AFP-L3 was 0.886 (95% CI: 0.809–0.963, P < 0.001). ROC curves indicated that the optimal threshold values for ONTD or AWD by AFP-L2 and AFP-L3 were 1.467 multiple of the median (MoM) and 1.944 MoM. The corresponding sensitivity, specificity and Youden index for AFP-L2 and AFP-L3 were 0.703, 0.947, 0.650 and 0.730, 0.974, 0.703, respectively. ConclusionAFP-L2 and AFP-L3 are favorable biomarkers for screening ONTD and AWD fetuses, and the risk model using AFP-L2 and AFP-L3 is of superior sensitivity and specificity.

Prenatal Genetic Diagnosis of Congenital Nephrotic Syndrome

Congenital nephrotic syndrome (CNS) of the Finnish type is an autosomal recessive disorder caused by mutations in the gene encoding nephrin (NPHS1). A 31-year-old primigravida woman from the Philippines was referred to Seoul St. Mary’s Hospital with an abnormally elevated maternal serum α-fetoprotein (MSAFP) level of 8.5 multiples of the median (MoM) at 16+1 weeks gestation. The MSAFP level was 11.25 MoM when measured at Seoul St. Mary’s Hospital. The amniotic fluid tested negative for acetylcholine esterase and had an α-fetoprotein level of 41.09 MoM. The karyotype was normal. Analysis of the NPHS1 gene in amniotic fluid by massively parallel sequencing revealed mutations associated with CNS. Cesarean delivery was performed at 37+4 weeks gestation due to transverse presentation. The neonate was not severely affected; there was no evidence of proteinuria or renal failure. However, because symptoms usually appear within 2 weeks to 1 month of age, close monitoring that includes regular blood and urine testing should be conducted.

Diagnosis and Management of Placental Mesenchymal Disease. A Review of the Literature.

To review what is currently known about placental mesenchymal dysplasia (PMD) including imaging techniques for diagnosis and differentiation from a molar pregnancy, genetics, maternal/fetal effects, and management. A literature search by research librarians at 2 universities was undertaken using the search engines PubMed and Web of Science. The search terms used were "etiology" OR "cause" OR "risk" OR "risks" OR "epidemiology" OR "diagnosis" OR "therapy" OR "prognosis" OR "management" AND "placental mesenchymal dysplasia" OR "placenta" AND "mesenchymal dysplasia." No limit was put on the number of years searched. The etiology of PMD remains uncertain, although there are a number of theories on causation. An elevated maternal serum α-fetoprotein level, slightly elevated human chorionic gonadotropin level, normal karyotype, multicystic lesions on ultrasound, and varying degrees of flow within cysts using color Doppler (stained-glass appearance) are helpful in making the diagnosis. On pathologic examination of the placenta, PMD is differentiated from molar pregnancy by the absence of trophoblastic hyperplasia. Fetal complications of PMD include hematologic disorders, Beckwith-Wiedemann syndrome, liver tumors, fetal growth restriction, preterm delivery, and intrauterine fetal demise. Maternal complications include gestational hypertension, preeclampsia, HELLP (hemolysis, elevated liver function tests, low platelets) syndrome, and eclampsia. Accurate diagnosis of PMD is imperative for appropriate management and surveillance to minimize adverse maternal and fetal outcomes. The importance of a correct diagnosis of PMD is important because it can be misdiagnosed as a partial molar pregnancy or a complete mole with coexisting normal fetus, and this can result in inappropriate management.

Combined second trimester maternal serum α-fetoprotein and uterine artery Doppler in the prediction of pre-eclampsia

Objective The objective was to evaluate the combination of second trimester maternal serum α-fetoprotein (MSAFP) and uterine artery Doppler (UAD) as a tool for the prediction of pre-eclampsia (PE). Background PE is a complex multisystem disease and the main cause of fetomaternal morbidity and mortality. The ultimate aim of antenatal care is to identify women at high risk and provide them with prophylactic treatment. No single test has emerged as a front runner and screening based on risk factors has low sensitivity. This has highlighted the need for an alternative. Patients and methods A prospective study on a total of 297 pregnant women had MSAFP measured between 15 and 19 weeks gestation and UAD measured between 19 and 21 weeks of gestation. Resistance index, pulsatility index (PI), and the presence of notches were measured. Receiver operator characteristic curves were created for MSAFP and UAD alone and in combination and then the outcomes were compared. The study was carried out at the Department of Obstetrics and Gynecology of the Faculty of Medicine, Menoufia University and Nasr City Police Hospital during a period from June 2016 to June 2017. Result A total of 17 women developed PE. The sensitivity of using UAD (resistance index) was 70.59% and for MSAFP was 52.94%. The combined sensitivity of UAD and MSAFP was 64.7% Conclusion The combination of MSAFP with UAD did not improve the screening efficacy for the prediction of PE and UAD performed significantly better as a stand-alone test.

Health economic evaluation of five prenatal screening strategies for Down's syndrome

Objective To investigate the cost-effectiveness and cost-benefit of five screening strategies for Down syndrome (DS) to optimize prenatal screening strategy. Methods A retrospective analysis was conducted in 26 803 gravidas, who underwent the second trimester maternal serum screening ( maternal serum α-fetoprotein and β-human chorionic gonadotropin) from 2002 to 2003, whom were classified into three groups according to the results of serum DS screening: high risk group (≥1/270), borderline risk group (≥1/1 000-<1/270) and elderly gravida group (age at expected date of confinement≥35 years old). TreeAge Pro 2011 sofware was used to set up the decision tree model for cost-effectiveness and cost-benefit analysis. Strategy 1: Maternal serum screening was carried out on all gravidas, and then prenatal diagnosis was performed for women in high risk group. Strategy 2: Non-invasive prenatal testing (NIPT) was carried out on all gravidas, and then prenatal diagnosis was offered for women with positive or suspected results. Strategy 3: NIPT was only carried out on gravidas of advanced maternal age and maternal serum screening was performed on the rest population. Gravidas with positive or suspected positive results in NIPT or classified into the high risk group underwent prenatal diagnosis. Strategy 4: Maternal serum screening was carried out on all gravidas. Those at high risk received prenatal diagnosis, while those at borderline risk underwent NIPT first and followed by prenatal diagnosis if positive or suspected positive NIPT results were identified. Strategy 5: Maternal serum screening was carried out on all gravidas. Those at high or borderline risk would undergo NIPT followed by prenatal diagnosis if they were positive or suspected positive for NIPT. Results (1) Among 26 803 gravidas, 1 244 were at high risk group (4.64%) with five having trisomy 21; 3 925 were at bordelrine risk (14.64%) with four having trisomy 21; 300 women were of advanced age (1.12%) with one having trisomy 21. (2) Cost-effectiveness analysis: the incremental cost-effectiveness ratios of strategy 3 and 4 were negative and that of strategy 1 was 0 with a cost-effectiveness ratio of 15 833 764.53. The incremental cost-effectiveness ratio of strategy 2 was 49 865 746.10, which was far greater than that of strategy 5 (63 049.56). The cost-effectiveness ratio of strategy 4 is 586 703.63, which was less than those of strategy 1,2 and 3 but higher than that of strategy 5. The average cost-effectiveness ratio of strategy 5 was the lowest (508 431.20) among these five strategies, which meant that for every diagnosis of DS, strategy 5 had the lowest cost (508 400 yuan). (3) Cost-benefit analysis: The benefits of strategy 4 and 5 were greater than their costs. Strategy 5 had the highest benefit-cost ratio, followed by strategy 4, 2, 3 and 1. (4) When other factors remained unchanged and only the acceptance rate of prenatal diagnosis was adjusted from 50% to 100%, strategy 1 had the least cost expectation, followed by strategy 3, 5, 4 and 2. When the cost of NIPT was below 82.4 yuan, the cost expectation of strategy 2 that performed on all gravidas was the lowest, while when it was between 82.4 and 1 827.2 yuan, the screening cost of strategy 5 was the lowest. Conclusions Strategy 5 has the best cost-effectiveness and cost-benefit. It would be the best screening strategy for DS, if the cost of NIPT is between 82.4-1 827.2 yuan. Key words: Down syndrome; Neonatal screening; Prenatal diagnosis; Costs and cost analysis; Cost-benefit analysis; High-throughput nucleotide sequencing

Case 2: A Patient with Trisomy 21, Transient Abnormal Myelopoiesis, and Pneumoperitoneum

A 34-week-gestation male infant is born appropriate for gestational age to a 41-year-old gravida 3, para 3 woman. The patient’s mother had received limited prenatal care starting at 15 weeks, and is found to have a positive result on maternal serum α-fetoprotein screening test and an amniocentesis that confirms trisomy 21 (47,XY+21 karyotype) with no evidence of translocation or mosaicism. The infant is born at an outside hospital and has physical features characteristic of trisomy 21. He is transferred to our facility for respiratory distress and multiple episodes of apnea and bradycardia on the day of birth. Sepsis is ruled out on admission. His initial complete blood cell count is significant for a white blood cell count of 15,300/μL (15.3×109/L) with 25% blasts. He is also noted to have an enlarged liver that is 1 cm below the costal margin. Peripheral blood smear and flow cytometry findings are consistent with a diagnosis of transient abnormal myelopoiesis (TAM). Pediatric hematology is consulted and recommends complete blood cell counts which are obtained regularly until day 22 after birth, when the TAM spontaneously resolves. The infant is able to receive full enteral feedings until he develops abdominal distention and irritability on day 12 after birth. An abdominal radiograph is notable for pneumoperitoneum concerning for an acute bowel perforation without signs of …

Gastroschisis: A Review of Management and Outcomes.

We performed an evidence-based review of the obstetrical management of gastroschisis. Gastroschisis is an abdominal wall defect, which has increased in frequency in recent decades. There is variation of prevalence by ethnicity and several known maternal risk factors. Herniated intestinal loops lacking a covering membrane can be identified with prenatal ultrasonography, and maternal serum α-fetoprotein level is commonly elevated. Because of the increased risk for growth restriction, amniotic fluid abnormalities, and fetal demise, antenatal testing is generally recommended. While many studies have aimed to identify antenatal predictors of neonatal outcome, accurate prognosis remains challenging. Delivery by 37 weeks appears reasonable, with cesarean delivery reserved for obstetric indications. Postnatal surgical management includes primary surgical closure, staged reduction with silo, or sutureless umbilical closure. Overall prognosis is good with low long-term morbidity in the majority of cases, but approximately 15% of cases are very complex with complicated hospital course, extensive intestinal loss, and early childhood death.

Changes in antimüllerian hormone levels in early pregnancy are associated with preterm birth

To determine the association of preterm birth with antimüllerian hormone (AMH) levels both in isolation and in combination with other markers of fetoplacental health commonly measured during integrated prenatal screening (IPS) for aneuploidy. Retrospective case-control study. Not applicable. Pregnant women in Iowa who elected to undergo IPS and who subsequently delivered in Iowa, including women giving birth at <37 weeks' gestation and controls who delivered at ≥37 weeks' gestation. None. Probability of a preterm birth. Second trimester AMH levels were not associated with preterm birth, either independently or after controlling for other markers of fetoplacental health. The AMH difference was not associated with preterm birth when modeled alone, but a statistically significant association was found after adjusting for maternal serum α-fetoprotein (MSAFP) and maternal weight change between the first and second trimesters. After stratifying the model by MSAFP level, most of the risk for preterm birth was identified in women with an MSAFP >1 multiple of the median and who had a stable or rising AMH level in early pregnancy. A lack of decline in the AMH level in early pregnancy can be used to identify women with a high probability for preterm birth, especially when MSAFP levels are >1 multiple of the median. Monitoring changes in the AMH level between the first and second trimesters of pregnancy may help identify women who would benefit from interventional therapies such as supplemental progesterone.

State-offered ethnically targeted reproductive genetic testing.

report on a program that involves state-offered carrier screening for cystic fibrosis, spinal mus-cular atrophy, and fragile X for the entire population of Israel, with screening for a wide array of additional diseases selected based on a combination of ethnicity, religious affiliation, and locality of origin. To their credit, Zlotogora et al.

Pregnancy in an NTBC‐Treated Patient With Hereditary Tyrosinemia Type I

Pregnancy in an NTBC‐Treated Patient With Hereditary Tyrosinemia Type I

Elevated maternal serum α-fetoprotein after minor trauma during pregnancy may predict adverse fetal outcomes.

We evaluated the relationship between minor trauma during pregnancy and elevated maternal serum α-fetoprotein level. This is a retrospective review of pregnant patients admitted to Fukui Prefectural Hospital with trauma during a 10-year period. Charts were reviewed for maternal age, gestational age, injury characteristics, Injury Severity Score, the presence of abdominal pain, systolic pressure and heart rate on arrival, fetal hemoglobin level, and maternal serum α-fetoprotein (MSAFP) concentration on arrival. Fifty-one pregnant patients with any trauma were treated at Fukui Prefectural Hospital. All patients were hemodynamically stable and had minor trauma. An adverse pregnancy outcome occurred in three patients (5%). One patient's fetus had a left kidney injury. Intrauterine fetal death occurred in two patients. The time from injury to fatal death was 180 minutes in one patient and 18 hours in the other patient. The mean ± SD fetal hemoglobin was 0.57% ± 0.88%. The mean ± SD MSAFP was 511 ng/mL ± 1,263 ng/mL. Three patients with adverse pregnancy outcome had a high MSAFP of greater than 1,000 ng/mL. High level of MSAFP may be a predictor of poor fetal outcome following trauma during pregnancy regardless of the severity of the trauma or the mother's hemodynamic status. Epidemiologic study, level V.

Maternal plasma levels of cell-free β-HCG mRNA as a prenatal diagnostic indicator of placenta accrete

ObjectiveSeveral biomarkers, including maternal serum creatinine kinase and α-fetoprotein, have been described as potential tools for the diagnosis of placental abnormalities. This study aimed to determine whether maternal plasma mRNA levels of the β subunit of human chorionic gonadotropin (β-HCG) could predict placenta accreta prenatally. MethodsSixty-eight singleton pregnant women with prior cesarean deliveries (CDs) were classified into three groups: normal placentation (35 women, control group); placenta previa alone (21 women, placenta previa group); and both placenta previa and placenta accreta (12 women, placenta previa/accreta group). Maternal plasma concentrations of cell-free β-HCG mRNA were measured by real-time reverse-transcription polymerase chain reaction and were expressed as multiples of the median (MoM). ResultsCell-free β-HCG mRNA concentrations (MoM, range) were significantly higher in women with placenta accreta (3.65, 2.78–7.19) than in women with placenta previa (0.94, 0.00–2.97) or normal placentation (1.00, 0.00–2.69) (Steel–Dwass test, P < 0.01 and P < 0.01, respectively). In the placenta previa/accreta group, the concentration of cell-free β-HCG mRNA was significantly higher among women who underwent CDs with hysterectomy (4.41, 3.49–7.19) than among women whose CDs did not result in hysterectomy (3.20, 2.78–3.70) (Mann–Whitney U test, P = 0.012). DiscussionAn increased level of cell-free β-HCG mRNA in the maternal plasma of women with placenta accreta may arise from direct uteroplacental transfer of cell-free placental mRNA molecules. ConclusionsThe concentration of cell-free β-HCG mRNA in maternal plasma may be applicable to the prenatal diagnosis of placenta accreta, especially to identify women with placenta accreta likely to require hysterectomy.

Is MSAFP Still a Useful Test for Detecting Open Neural Tube Defects and Ventral Wall Defects in the Era of First-Trimester and Early Second-Trimester Fetal Anatomical Ultrasounds?

Introduction: To evaluate whether maternal serum α-fetoprotein (MSAFP) improves the detection rate for open neural tube defects (ONTDs) and ventral wall defects (VWD) in patients undergoing first-trimester and early second-trimester fetal anatomical survey. Material and Methods: A cohort of women undergoing screening between 2005 and 2012 was identified. All patients were offered an ultrasound at between 11 weeks and 13 weeks and 6 days of gestational age for nuchal translucency/fetal anatomy followed by an early second-trimester ultrasound at between 15 weeks and 17 weeks and 6 days of gestational age for fetal anatomy and MSAFP screening. All cases of ONTD and VWD were identified via query of billing and reporting software. Sensitivity and specificity for detection of ONTD/VWD were calculated, and groups were compared using the Fisher exact test, with p < 0.05 as significance. Results: A total of 23,790 women met the criteria for inclusion. Overall, 15 cases of ONTD and 17 cases of VWD were identified; 100% of cases were diagnosed by ultrasound prior to 18 weeks' gestation; none were diagnosed via MSAFP screening (p < 0.001). First-trimester and early second-trimester ultrasound had 100% sensitivity and 100% specificity for diagnosing ONTD/VWD. Discussion: Ultrasound for fetal anatomy during the first and early second trimester detected 100% of ONTD/VWD in our population. MSAFP is not useful as a screening tool for ONTD and VWD in the setting of this ultrasound screening protocol.

Is There an Association Between Placenta Previa and Serum Analytes?

INTRODUCTION: The objective of this study was to evaluate the association between maternal serum analytes and placenta previa. METHODS: Chart review of deliveries from 2004 to 2012 with two comparison groups: placenta previa without accreta and a control group. Patients in the control group were randomly selected from deliveries without placenta previa. Patients with previa were confirmed by third-trimester ultrasonography. Exclusion criteria were placenta previa with pathology-confirmed accreta, multiple gestations, fetal anomalies, or growth restriction. Primary outcomes were maternal serum analytes in the first trimester: pregnancy-associated plasma protein A and free β-human chorionic gonadotropin (β-hCG), and second trimester: α-fetoprotein), free β-hCG, unconjugated estriol, and inhibin. RESULTS: Twenty-six women with previa met inclusion criteria and 43 women in the control group. The groups did not differ with respect to maternal age, gravidity, or parity. Alpha-fetoprotein multiples of the median was significantly higher in women with previa cases than women in the control group (P<.005). Pregnancy-associated plasma protein A multiples of the median was higher (but was not statistically significant) in women with previa than in the women in the control group (P<.064). There were no differences between groups with respect to first-trimester free β-hCG, second-trimester free β-hCG, unconjugated estriol, or inhibin (Table 1). The following analytes were not available on all specimens: second-trimester free β-hCG, unconjugated estriol, and inhibin.CONCLUSIONS: In our women with placenta previa, maternal serum α-fetoprotein was significantly higher than in women in the control group. We also observed higher levels of pregnancy-associated plasma protein A in women with previa but this did not reach statistical significance. Prospective studies are needed to confirm these findings and determine the relationship with pregnancy outcome.

The Triple Test

Featured article: Wald NJ, Cuckle HS, Densem JW, Nanchahal K, Royston P, Chard T, et al. Maternal serum screening for Down's syndrome in early pregnancy. BMJ 1988;297:883–7.2 The era of organized prenatal screening began in the mid-1970s with the discovery that maternal serum α-fetoprotein (AFP)3 could be used as a screening test for neural tube defects. This discovery led to work on how screening performance could be determined from AFP distributions in affected and unaffected pregnancies. To this end, the multiple of the median (MoM) was created (1) to allow for systematic interlaboratory AFP assay variation and factors such as gestational age. The multiple of the median was used in the 1977 UK Collaborative Study on Alpha-Fetoprotein in Relation to Neural-Tube Defects (2) and in a 1984 report on using low AFP concentrations in conjunction with maternal age in screening for Down syndrome (3). It was also used in our 1988 study described in the featured report. We combined AFP, unconjugated estriol, and human chorionic gonadotropin with maternal age to produce an estimate of the risk of having a Down syndrome pregnancy. This report …

A meningomyelocele with normal intracranial signs on ultrasound and false-negative amniotic fluid alpha-fetoprotein and acetylcholinesterase

Neural tube defects are the major targets of prenatal diagnoses, along with Down syndrome. Prenatal diagnosis of spina bifida is possible at second trimester of gestation through α-fetoprotein and acetylcholinesterase biochemistry assays and ultrasound. In particular, the discovery of characteristic intracranial signs on ultrasound leads to a very high diagnosis rate. However, it is rare for spina bifida to present without intracranial signs while also showing normal values of maternal serum α-fetoprotein, amniotic fluid α-fetoprotein, and acetylcholinesterase. In our hospital, a fetus with spina bifida was delivered at 37+5 weeks' gestation by cesarean section, and was continually followed up over 2 years to date.

Index of Suspicion in the Nursery

A 37-week female infant is born via cesarean delivery due to preeclampsia to a 26-year-old G1 mother. All maternal serologic test results are within normal limits. The pregnancy was complicated by maternal primary generalized epilepsy treated with valproic acid (VPA) and supplemented with folic acid, mild thrombocytopenia attributed to VPA therapy, and increased maternal serum α-fetoprotein level at 17 weeks. Antenatal ultrasound reveals a lumbosacral myelomeningocele and Chiari II malformation. After birth, the infant is noted to have a midline sacral defect and is positioned side-lying. She has mild respiratory distress that improves with continuous positive airway pressure. Apgar scores are 7 and 8 at 1 and 5 minutes, respectively. She is transitioned to a high-humidity nasal cannula and transported to the NICU for further management. On physical examination, the patient’s birthweight is 2.79 kg (25th percentile), length is 51 cm (90th percentile), and head circumference is 29.5 cm (<3rd percentile). She has close-set eyes, a prominent glabella, and epicanthal folds. Her ears are normal in size and position. Her anterior fontanelle is slightly full, with sagittal sutures splayed 1 cm. Her palate is intact, with gag and suck present. Her heart has a regular rate and rhythm with no murmur appreciated. Pulses and perfusion are normal, and breath sounds are clear with moderate aeration. Her abdomen is soft, nontender, and nondistended, with no hepatosplenomegaly. She has spontaneous movement bilaterally at her hips, knees, and ankles. Her spinal defect is located over the lumbosacral area and is 2 cm × 1 cm, with moist reddish-purplish tissue. A 1-cm rim of hemangiomatous tissue is present at the superior and lateral aspects of the lesion. The patient has normal Tanner 1 female genitalia. Anus is patent with anal wink reflex present. She has long thumbs bilaterally with low-set, inverted, and widely spaced …