Cracking the code: interpreting content and phrases used in maternal-fetal medicine fellowship letters of recommendation.

BACKGROUND: Letters of recommendation for Maternal-Fetal Medicine(MFM) fellowship are a critical part of the applicant selection process. However, data regarding best practices for how to write LOR for MFM is limited. Similarly, within letters of recommendation, differences in the "code" or meaning of summative words/phrases used at the end of letters of recommendation are seen between surgery, pediatrics, and medicine. However, data regarding code MFM Letters of recommendation are quite limited. OBJECTIVE: We sought to describe what Maternal-Fetal Medicine program directors value in letters of recommendation for fellowship applicants and how PDs interpret commonly used summative words/phrases. STUDY DESIGN: After IRB exemption, subject matter experts developed an e-survey querying the importance of various letters of recommendation "best practices" described by other specialties. Content and face validation were performed prior to dissemination. This cross-sectional survey was administered to MFM program directors in February 2023. The primary outcome was the relative importance of letters of recommendation content areas. Secondary outcomes included the strength of each summative "code" phrase. Descriptive analysis was performed and principal component analysis (PCA) was then used to reduce the list of phrases to their underlying dimensions. Statistical analysis was performed by SPSS 29.0. RESULTS: Of 104 MFM program directors sent the survey, 70 (67%) responded. MFM program directors reviewed an average of 78 applications (SD, 30) with 60% writing ≥3 letters/year. Ninety-one percent of respondents noted that letters of recommendation are important/very important in shaping impressions of an applicant. Respondents reported the depth of interaction with an applicant, the applicant's specific behavior traits, the applicant's abilities and a summative statement including strength of the recommendation as important content for MFM fellowship letters of recommendation. Letter length, use of bold/italics, and restating the applicant's curriculum vitae were considered not important. Following PCA with varimax rotation, 14 specific phrases used in letters of recommendation were reduced to 5 themes: high qualitative assessments, average qualitative assessments, objective metrics, exceeding expectations and grit. These themes accounted for 64.6% of the variance in the model (KMO 0.7, Bartlett's Test of Sphericity p<.01). Phrases that respondents considered positive included: "Top 5%," "Want to keep," and "highest recommendation," (all mean score≥4.5/5), while "expected level," "showed improvement," and "2nd quartile" were negatively associated code words (all mean score <2.5/5). CONCLUSION: MFM program directors reported that descriptions of an applicant's abilities, behavior traits, and depth of the writer's interactions with the applicant were all important components of an MFM fellowship letters of recommendation. Letter length, bold/italics, and highlights from the CV were not important. A clear "code" emerged regarding summative phrases included in letters of recommendation. Dissemination of these data might help less experienced letter writers send a clearer message and ensure all letter writers have a shared mental model.

Perinatal outcomes according to umbilical artery Doppler assessment among fetuses with congenital heart disease.

PURPOSE: To evaluate a cohort of fetuses with congenital heart disease (CHD) who underwent serial umbilical artery (UA) Doppler surveillance and assess perinatal outcome according to UA Doppler assessment. METHODS: A retrospective cohort study of singleton fetuses with CHD at a single academic center was performed between 2018 and 2020. Fetuses with a chromosomal abnormality or growth restriction were excluded. We compared fetuses with normal versus abnormal UA Doppler assessment at any time in pregnancy. Abnormal UA Doppler assessment was defined as decreased end diastolic flow, determined by an elevated systolic/diastolic ratio >95th percentile for gestational age, or absent/reversed end diastolic flow. Logistic regression assessed the odds of fetuses with CHD and abnormal UA Doppler assessment having a composite adverse perinatal (defined as fetal, neonatal, or infant death), adjusting for relevant covariates. RESULTS: We identified a cohort of 171 fetuses with CHD that met inclusion criteria. Of these, 154 (90%) had normal UA Doppler assessment and 17 (10%) had abnormal UA Doppler assessment throughout pregnancy. Maternal characteristics did not differ between groups except for maternal race and history of preeclampsia. There was no statistically significant difference in primary outcome between groups [14% (21/154) of fetuses with normal UA Doppler assessment had an adverse perinatal outcome compared to 24% (4/17) of those with abnormal UA Doppler assessment, p = 0.28]. CONCLUSION: UA Doppler assessment is unlikely to predict adverse perinatal outcome in normally grown, euploid singleton fetuses with CHD.

Cell-Free DNA Screening for Single-Gene Disorders.

Importance: In pregnancy, cell-free DNA (cfDNA) represents short fragments of placental DNA released into the maternal blood stream through natural cell death. Noninvasive prenatal screening with cfDNA is commonly used in pregnancy to screen for common aneuploidies. This technology continues to evolve, and laboratories now offer cfDNA screening for single-gene disorders. Objective: This article aims to review cfDNA screening for single-gene disorders including the technology, current syndromes for which screening may be offered, limitations, and current recommendations. Evidence Acquisition: Original research articles, review articles, laboratory white papers, and society guidelines were reviewed. Results: Cell-free DNA screening for single-gene disorders is not currently recommended by medical societies. There may be a role in specific circumstances and only after comprehensive pretest counseling. It can be considered in the setting of some fetal ultrasound anomalies, and usually only after diagnostic testing is offered and declined. Conclusions: Given the limitations of using cfDNA screening for single-gene disorders, caution is recommended when considering these tests. It should only be offered with involvement of a reproductive genetic counselor, medical geneticist, or maternal fetal medicine specialist to ensure comprehensive counseling and appropriate utilization.

A Large Thyroid Goiter in a Newborn With Congenital Hypothyroidism: Timeline for Decrease in Size of Thyroid.

Congenital hypothyroidism rarely causes a clinically significant neck mass in newborns. We present the case of a newborn with congenital hypothyroidism and significantly enlarged goiter and discuss imaging considerations and medical and surgical management. This infant was prenatally discovered to have a midline neck mass on 28 week ultrasound measuring 6.0 cm × 3.4 cm × 5.8 cm. Diagnostic cordocentesis demonstrated elevated thyroid-stimulating hormone (TSH, 361 µIU/mL). Maternal evaluation for thyroid disease and antithyroid antibodies was negative. A Cesarean section at 38 weeks gestation was recommended due to hyperextension of the fetal neck. The infant was intubated for respiratory distress. Postnatal magnetic resonance imaging revealed a 5.5 cm × 4.4 cm × 7.6 cm goiter and laboratory studies confirmed the diagnosis of primary hypothyroidism (TSH 16.7 µIU/mL). Treatment was initiated with intravenous levothyroxine and transitioned to oral supplementation. Serial ultrasounds showed decreased goiter volume over several weeks, with recent volume per lobe being 22% and 44% of original volume. This case demonstrates the importance of prompt diagnosis and initiation of thyroid hormone replacement, allowing for significant goiter regression without surgical intervention and ensuring normal growth and neurodevelopmental outcome. Surgical management should be considered for those with persistent compressive symptoms despite optimal medical management.

Risk Factors for Adverse Maternal Outcomes among Patients with Severe Preeclampsia Before 34 Weeks.

OBJECTIVE: This study aimed to characterize rates of maternal morbidity associated with early (<34 wk) preeclampsia with severe features and to determine factors associated with developing these morbidities. STUDY DESIGN: Retrospective cohort study of patients with early preeclampsia with severe features at a single institution from 2013 to 2019. Inclusion criteria were admission between 23 and 34 weeks and diagnosis of preeclampsia with severe features. Maternal morbidity defined as death, sepsis, intensive care unit (ICU) admission, acute renal insufficiency (acute kidney injury [AKI]), postpartum (PP) dilation and curettage, PP hysterectomy, venous thromboembolism (VTE), PP hemorrhage (PPH), PP wound infection, PP endometritis, pelvic abscess, PP pneumonia, readmission, and/or need for blood transfusion. Death, ICU admission, VTE, AKI, PP hysterectomy, sepsis, and/or transfusion of >2 units were considered severe maternal morbidity (SMM). Simple statistics used to compare characteristics among patients experiencing any morbidity and those not. Poisson regression used to assess relative risks. RESULTS: Of 260 patients included, 77 (29.6%) experienced maternal morbidity and 16 (6.2%) experienced severe morbidity. PPH (n = 46, 17.7%) was the most common morbidity, although 15 (5.8%) patients were readmitted, 16 (6.2%) needed a blood transfusion, and 14 (5.4%) had AKI. Patients who experienced maternal morbidity were more likely to be advanced maternal age, have preexisting diabetes, have multiples, and deliver nonvaginally (all ps < 0.05). Diagnosis of preeclampsia < 28 weeks or longer latency from diagnosis to delivery were not associated with increased maternal morbidity. In regression models, the relative risk of maternal morbidity remained significant for twins (adjusted odds ration [aOR]: 2.57; 95% confidence interval [CI]: 1.67, 3.96) and preexisting diabetes (aOR: 1.64; 95% CI: 1.04, 2.58), whereas attempted vaginal delivery was protective (aOR: 0.53; 95% CI: 0.30, 0.92). CONCLUSION: In this cohort, more than 1 in 4 patients diagnosed with early preeclampsia with severe features experienced maternal morbidity, whereas 1 in 16 patients experienced SMM. Twins and pregestational diabetes were associated with higher risk of morbidity, whereas attempted vaginal delivery was protective. These data may be helpful in promoting risk reduction and counseling patients diagnosed with early preeclampsia with severe features. KEY POINTS: · One in four patients diagnosed with preeclampsia w/ severe features experienced maternal morbidity.. · One in 16 patients with preeclampsia w/ severe features experienced severe maternal morbidity.. · Factors most associated with morbidity/severe morbidity were twins and pregestational diabetes.. · Patients who attempted vaginal delivery appeared to have a lower rate of morbidity..

Maternal and peripartum risk factors for acute funisitis among term deliveries complicated by intraamniotic infection.

BACKGROUND: Acute funisitis-the histologic diagnosis of inflammation within the umbilical cord-represents a fetal inflammatory response and has been associated with adverse neonatal outcomes. Little is known regarding the maternal and intrapartum risk factors associated with the development of acute funisitis among term deliveries complicated by intraamniotic infection. OBJECTIVE: This study aimed to identify the maternal and intrapartum risk factors associated with developing acute funisitis among term deliveries complicated by intraamniotic infection. STUDY DESIGN: After institutional review board approval, we conducted a retrospective cohort study of term deliveries affected by clinical intraamniotic infection at a single tertiary center between 2013 and 2017, with placental pathology consistent with histologic chorioamnionitis. The exclusion criteria included intrauterine fetal demise, missing delivery information or placental pathology, and documented congenital fetal abnormalities. Maternal sociodemographic, antepartum, and intrapartum factors were compared among patients with acute funisitis on pathology to those without acute funisitis using bivariate statistics. Regression models were developed to estimate the adjusted odds ratios. RESULTS: Of 123 patients meeting the inclusion criteria, 75 (61%) had acute funisitis on placental pathology. Compared with placental specimens without acute funisitis, acute funisitis was observed more frequently among patients with maternal BMI ≥30 kg/m2 (58.7% vs 39.6%, P=.04) and labor courses with increased rupture of membrane duration (17.3 vs 9.6 hours, P=.001). Use of fetal scalp electrode was observed less frequently in acute funisitis (5.3% vs 16.7%, P=.04) than cases without acute funisitis. In regression models, maternal BMI ≥30 kg/m2 (adjusted odds ratio, 2.67; 95% confidence interval, 1.21-5.90) and rupture of membrane >18 hours (adjusted odds ratio, 2.48; 95% confidence interval, 1.07-5.75) were significantly associated with acute funisitis. Fetal scalp electrode use (adjusted odds ratio, 0.18; 95% confidence interval, 0.04-0.71) was negatively associated with acute funisitis. CONCLUSION: In term deliveries with intraamniotic infection and histologic chorioamnionitis, maternal BMI ≥30 kg/m2, and rupture of membrane>18 hours were associated with acute funisitis on placental pathology. As insight into the clinical impact of acute funisitis grows, the ability to predict which pregnancies are at the greatest risk for its development may allow for a tailored approach to predicting neonatal risk for sepsis and related comorbidity.

Sex-Dependent Differences in Mouse Placental Gene Expression following a Maternal High-Fat Diet.

OBJECTIVE: In utero fetal exposures may have sex-specific placental gene responses. Our objective was to measure sex-based differences in placental gene expression from dams fed high-fat diet (HFD) versus control diet (CD). STUDY DESIGN: We fed timed pregnant Friend virus B-strain dams either a CD (n = 5) or an HFD (n = 5). We euthanized dams on embryonic day 17.5 to collect placentas. We extracted placental RNA and hybridized it to a customized 96-gene Nanostring panel focusing on angiogenic, inflammatory, and growth genes. We compared normalized gene expression between CD and HFD, stratified by fetal sex, using analysis of variance. Pathway analysis was used to further interpret the genomic data. RESULTS: Pups from HFD-fed dams were heavier than those from CD-fed dams (0.97 ± 0.06 vs 0.84 ± 0.08 g, p < 0.001). Male pups were heavier than females in the HFD (0.99 ± 0.05 vs 0.94 ± 0.06 g, p = 0.004) but not CD (0.87 ± 0.08 vs 0.83 ± 0.07 g, p = 0.10) group. No sex-based differences in placental gene expression in CD-fed dams were observed. Among HFD-fed dams, placentas from female pups exhibited upregulation of 15 genes (q = 0.01). Network analyses identified a cluster of genes involved in carbohydrate metabolism, cellular function and maintenance, and endocrine system development and function (p = 1 × 10-23). The observed female-specific increased gene expression following in utero HFD exposure was predicted to be regulated by insulin (p = 5.79 × 10-13). CONCLUSION: In female compared with male pups, in utero exposure to HFD upregulated placental gene expression in 15 genes predicted to be regulated by insulin. Sex-specific differences in placental expression of these genes should be further investigated. KEY POINTS: · Male pups were heavier than female pups at the time of sacrifice when dams were fed an HFD.. · HFD was associated with upregulated gene expression in female placentas.. · Female-specific increased gene was predicted to be regulated by insulin..

The Association between Placenta Accreta Spectrum Severity and Incidence of Small for Gestational Age Neonates.

OBJECTIVE: The aim of the study is to evaluate whether pathologic severity of placenta accreta spectrum (PAS) is correlated with the incidence of small for gestational age (SGA) and neonatal birthweight. STUDY DESIGN: This was a multicenter cohort study of viable, non-anomalous, singleton gestations delivered with histology-proven PAS. Data including maternal history, neonatal birthweight, and placental pathology were collected and deidentified. Pathology was defined as accreta, increta, or percreta. The primary outcome was rate of SGA defined by birth weight less than the 10th percentile. The secondary outcomes included incidence of large for gestational age (LGA) babies as defined by birth weight greater than the 90th percentile as well as incidence of SGA and LGA in preterm and term gestations. Statistical analysis was performed using Chi-square, Kruskal-Wallis, and log-binomial regression. Increta and percreta patients were each compared with accreta patients. RESULTS: Among the cohort of 1,008 women from seven United States centers, 865 subjects were included in the analysis. The relative risk (RR) of SGA for increta and percreta did not differ from accreta after adjusting for confounders (adjusted RR = 0.63, 95% confidence interval [CI]: 0.36-1.10 for increta and aRR = 0.72, 95% CI: 0.45-1.16 for percreta). The results were stratified by placenta previa status, which did not affect results. There was no difference in incidence of LGA (p = 1.0) by PAS pathologic severity. The incidence of SGA for all PAS patients was 9.2% for those delivered preterm and 18.7% for those delivered at term (p = 0.004). The incidence of LGA for all PAS patients was 12.6% for those delivered preterm and 13.2% for those delivered at term (p = 0.8203). CONCLUSION: There was no difference in incidence of SGA or LGA when comparing accreta to increta or percreta patients regardless of previa status. Although we cannot suggest causation, our results suggest that PAS, regardless of pathologic severity, is not associated with pathologic fetal growth in the preterm period. KEY POINTS: · PAS severity is not associated with SGA in the preterm period.. · PAS severity is not associated with LGA.. · Placenta previa does not affect the incidence of SGA in women with PAS..

Clinical Correlates of Placenta Accreta Spectrum Disorder Depending on the Presence or Absence of Placenta Previa: A Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate whether there are differences in risk factors and maternal outcomes of pregnancies complicated by placenta accreta spectrum depending on the presence or absence of placenta previa. DATA SOURCES: We performed a systematic search in Medline, EMBASE, ClinicalTrials.gov , and Web of Science from inception through April 25, 2022, without language or date restrictions. Search strategy included the key words "placenta accreta," "placenta increta," "placenta percreta," "adherent placenta," "invasive placenta," "abnormal placent*," "placenta previa," and "marginal placent*." METHODS OF STUDY SELECTION: Of the 1,122 articles screened, seven studies were included in the final review. Studies were included if they compared the risk factors and maternal outcomes of pregnancies complicated by placenta accreta spectrum depending on the presence or absence of placenta previa. TABULATION, INTEGRATION, AND RESULTS: A random-effects model was used to pool the mean differences or odds ratios (OR) and the corresponding 95% CIs using RevMan software. A total of 3,342 pregnancies complicated by placenta accreta spectrum were included in the meta-analysis (2,365 without previa and 977 with previa). Pregnancies complicated by placenta accreta spectrum without previa were more likely to have been conceived by in vitro fertilization (IVF) (OR 3.11, 95% CI 1.93-5.02, P <.001, I 2 =52.0%) and to be associated with prior dilation and curettage (D&C) (OR 1.60, 95% CI 1.15-2.22, P =.005, I 2 =0.0%) and myomectomy (OR 2.47, 95% CI 1.31-4.66, P =.005, I 2 =0.0%), but they were less likely to be associated with prior cesarean delivery (OR 0.15, 95% CI 0.06-0.37, P <.001, I 2 =87.0%). Placenta accreta spectrum without previa was less likely to be diagnosed antenatally (OR 0.07, 95% CI 0.04-0.11, P <.001, I 2 =38.0%). Also, women with pregnancies without previa had lower rates of red blood cell transfusion, intensive care unit admission, risk of hysterectomy, unscheduled delivery, and intraoperative bowel or bladder injuries. CONCLUSION: Pregnancies complicated by placenta accreta spectrum without previa had a more prominent association with IVF and prior D&C and myomectomy but were much less likely to be associated with prior cesarean delivery. Further, placenta accreta spectrum without previa was less likely to be diagnosed antenatally, although it had better maternal outcomes as compared with placenta accreta spectrum with previa. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42022307637.

Does acute funisitis predict worse neonatal outcomes among term newborns?

BACKGROUND: Acute funisitis-the histologic diagnosis of inflammation within the umbilical cord-represents a fetal inflammatory response to infection. Although acute funisitis has been associated with an increased risk of adverse outcomes among preterm neonates, there are limited and conflicting data with term deliveries. OBJECTIVE: This study aimed to evaluate the association between acute funisitis and neonatal morbidity in neonates born at term to pregnant patients with a clinical diagnosis of intraamniotic infection. STUDY DESIGN: This was a retrospective cohort study of pregnant patients who had clinically diagnosed intraamniotic infection at term, delivered vaginally at a single tertiary institution from 2013 to 2019, and had histologic chorioamnionitis on placental pathology. Patients with intrauterine fetal demise or missing neonatal/placental pathology data were excluded. The primary outcome was a neonatal sepsis composite, defined as culture-positive bacteremia, neutropenia (absolute neutrophil count<3500/µL), or immature-to-total neutrophil ratio>0.2. The secondary outcomes included composite neonatal morbidity, defined as neonatal intensive care unit admission, 5-minute Apgar score <7, bacteremia, endotracheal intubation or need for continuous positive airway pressure, intraventricular hemorrhage (grade 3 or 4), necrotizing enterocolitis (stage 3 or 4), umbilical artery pH<7.1, umbilical artery base excess>12, and neonatal mortality. The components of these composites, neonatal intensive care unit length of stay, and Kaiser early-onset sepsis score were also measured. Neonates with acute funisitis on pathology were compared with those without acute funisitis using bivariate statistics. Regression was used to estimate the relative risk of outcomes. RESULTS: Of 184 neonates with deliveries complicated by intraamniotic infection, acute funisitis was present in 109 (59%) placental specimens. Composite neonatal sepsis was significantly higher among neonates with acute funisitis (relative risk, 1.85; 95% confidence interval, 1.13-3.03) than in those without acute funisitis. As a marker for sepsis, acute funisitis has a sensitivity of 39.4%, negative predictive value of 47.2%, specificity of 78.7%, and positive predictive value of 72.9%. An immature-to-total neutrophil ratio>0.2 (relative risk, 1.83; 95% confidence interval, 1.09-3.08) was also significantly associated with acute funisitis. Neonatal morbidity composite, intraventricular hemorrhage, necrotizing enterocolitis, neonatal intensive care unit admission, higher Kaiser early-onset sepsis scores, and other examined outcomes were not statistically associated with acute funisitis. CONCLUSION: In term deliveries complicated by intraamniotic infection, acute funisitis was associated with increased neonatal sepsis. Current approaches for estimating neonatal sepsis risk are limited by their reliance on indirect maternal factors such as maximum maternal temperature and intrapartum antibiotic use. This study suggests that acute funisitis may serve as a marker that could be utilized to augment risk stratification at birth if a protocol for evaluating the umbilical cord in real-time were widely adopted.

Risk Factors for Adverse Maternal Outcomes following Expectantly Managed Preterm Prelabor Rupture of Membranes.

OBJECTIVE: We sought to characterize the incidence and risk factors associated with developing maternal morbidity following preterm prelabor rupture of membranes. STUDY DESIGN: Retrospective case-control study of patients with preterm prelabor rupture of membranes at a single institution from 2013 to 2019 admitted at ≥23 weeks gestational age. The primary outcome was a composite of maternal morbidity which included: death, sepsis, intensive care unit (ICU) admission, acute kidney injury, postpartum dilation and curettage, postpartum hysterectomy, venous thromboembolism, postpartum hemorrhage, postpartum wound complication, postpartum endometritis, pelvic abscess, postpartum pneumonia, readmission, and/or need for blood transfusion were compared with patients without above morbidities. Severe morbidity was defined as: death, ICU admission, venous thromboembolism, acute kidney injury, postpartum hysterectomy, sepsis, and/or transfusion >2 units. Demographics, antenatal, and delivery characteristics were compared between patients with and without maternal morbidity. Bivariate statistics and regression models were used to compare outcomes and calculate adjusted odd ratios. RESULTS: Of 361 included patients, 64 patients (17.7%) experienced maternal morbidity and nine (2.5%) had severe morbidity. Patients who experienced maternal morbidity were significantly (p < 0.05) more likely to be older, have private insurance, have BMI ≥40, have chorioamnionitis at delivery, and undergo cesarean or operative vaginal delivery when compared with patients who did not experience morbidity. After controlling for confounders, cesarean delivery (aOR 2.38, 95% CI[1.30,4.39]), body mass index ≥40 at admission (aOR 2.54, 95% CI[1.12,5.79]), private insurance (aOR 3.08, 95% CI[1.54,6.16]), and tobacco use (aOR 3.43, 95% CI[1.58,7.48]) were associated with increased odds of maternal morbidity. CONCLUSION: In this cohort, maternal morbidity occurred in 17.7% of patients with preterm prelabor rupture of membranes. Private insurance, body mass index ≥40, tobacco use, and cesarean delivery were associated with higher odds of morbidity. These data can be used in counseling and to advocate for smoking cessation. KEY POINTS: · 17.7% of patients with PPROM experienced maternal morbidity.. · BMI ≥40 was associated with higher odds of maternal morbidity.. · Tobacco use and cesarean delivery were associated with higher odds of maternal morbidity..

Accuracy of estimated fetal weight assessment in fetuses with abdominal wall defects.

BACKGROUND: Gastroschisis and omphalocele are congenital abdominal wall defects in which the bowel and other abdominal contents extrude from the fetal abdominal cavity. Standard formulas for estimated fetal weight using ultrasound include fetal abdominal circumference measurement and have a range of error of approximately 10%. It is unknown whether the accuracy of estimated fetal weight assessment is compromised in fetuses with abdominal wall defects because of the extrusion of abdominal contents. OBJECTIVE: This study aimed to assess the accuracy of standard estimated fetal weight assessment in fetuses with abdominal wall defects by comparing prenatal assessment of fetal weight with actual birthweight. STUDY DESIGN: A retrospective cohort study of fetuses diagnosed with gastroschisis or omphalocele was performed at a single center from 2012 to 2018. Fetuses with additional anomalies or confirmed chromosome abnormalities were excluded. Estimated fetal weight was calculated using the Hadlock formula. Published estimates of fetal growth rate were used to establish a projected estimated fetal weight at birth from the final growth ultrasound, and the percent difference between projected estimated fetal weight at birth and actual birthweight was calculated. The Wilcoxon rank-sum test was used to examine the difference between projected estimated fetal weight and actual birthweight. RESULTS: We had complete data for 112 fetuses with abdominal wall defects, including 85 with gastroschisis and 27 with omphalocele. The median (interquartile range) projected estimated fetal weight was similar to median birthweight, at 2283 g (interquartile range, 2000-2810) and 2306 g (interquartile range, 1991-264), respectively, which did not represent a statistically significant difference between projected estimated fetal weight and actual birthweight (P=.32). The median percent error was 6.8 (3.1-12.8). In addition, we did not find any statistical difference between projected estimated fetal weight and actual birthweight in patients with gastroschisis (P=.52) or omphalocele (P=.35) individually. Estimated fetal weight was underestimated in most cases (n=68 [60.7%]). CONCLUSION: In fetuses with abdominal wall defects, standard measurement of fetal weight shows an accuracy that is at least comparable with previously established margins of error for ultrasound assessment of fetal weight. Standard estimated fetal weight assessment remains an appropriate method of estimating fetal weight in these fetuses.

Effect of a High-Fat Diet and Metformin on Placental mTOR Signaling in Mice.

Objective This study was aimed to measure the effects of a high-fat diet and metformin on placental mechanistic target of rapamycin (mTOR) signaling in mice. Study Design Pregnant friend virus B (FVB)-strain mice were allocated on embryonic day (e) 0.5 to one of four groups; group 1: control diet (CD, 10% fat) + control treatment (CT), group 2: CD + metformin treatment (MT), group 3: high-fat diet (HFD, 60% fat) + CT, and group 4: HFD + MT. Metformin (2.5 mg/mL) was provided in water; CT mice received water. Fetuses and placentas were collected. Western blot measured placental p-Akt and p-S6 expression. Results 20 dams (five/group) and 192 fetuses were studied. Compared with CD-fed, HFD-fed dams had higher placental p-Akt protein expression ( p < 0.0001). Among HFD-dams, placental p-Akt was higher in metformin-treated compared with control-treated ( p < 0.001). Among CD-fed dams, there was no significant difference in placental p-S6 expression in MT versus CT groups. Among HFD-fed dams placental p-S6 expression was lower in those exposed to metformin-treated versus controls ( p = 0.001). Conclusion Increased placental mTOR signaling and metformin inhibition of placental mTOR signaling only occurred in the presence of an HFD exposure. These findings suggest that metformin may modulate placental mTOR signaling in the presence of metabolic exposures during pregnancy.

The Effect of Blood Loss on Cefazolin Levels in Women Undergoing Cesarean Delivery.

OBJECTIVE: To quantify the effects of operative blood loss during cesarean on tissue and plasma cefazolin concentrations. STUDY DESIGN: This was a prospective observational study of singleton pregnancies undergoing scheduled cesarean between 34 and 40 weeks. Cefazolin administered prior to skin incision. Maternal plasma samples were obtained (Time 1[T1]: immediately, T2: 20 minutes, T3: 40 minutes, and T4: 60 minutes after cefazolin infusion). Subcutaneous adipose tissue sampled before and after fascia. Primary outcome was subcutaneous adipose cefazolin level after fascial closure. Formal quantitative blood loss (QBL) performed. Women with higher QBL, those at/above 75% of QBL in this population, were compared with those with lower QBL (QBL below 75%). Data analyzed using bivariable statistics. RESULTS: Ninety-two women were screened, 32 were eligible, and 20 enrolled. Median QBL was 630 mL (interquartile range [IQR]: 473-818) and 1,160 mL (IQR: 1,000-1,560) in the low and high QBL groups, respectively. Demographics and operative characteristics were similar. Median adipose cefazolin level after fascial closure did not differ between the groups (3.5 vs. 3.9 µg/g, p = 0.75). No differences in maternal plasma cefazolin concentrations between the groups at any time point or in pharmacokinetic parameters were seen. CONCLUSION: Intraoperative maternal plasma concentrations and adipose levels of cefazolin are similar between women with high and low blood loss at the time of cesarean delivery.

Targeted Multiplex Gene Expression Profiling to Measure High-Fat Diet and Metformin Effects on Fetal Gene Expression in a Mouse Model.

BACKGROUND: Maternal obesity and excessive gestational weight gain (GWG) are associated with delivery of a large-for-gestational-age infant. We used a high-fat diet (HFD) mouse model to separate the effect of maternal obesity from excessive GWG on fetal growth. Our objective was to identify fetal gene expression changes in an HFD and control diet (CD) mouse model with and without metformin exposure. STUDY DESIGN: Normal weight timed-pregnant (Female Friend virus B) strain mice were allocated on day e0.5 to receive HFD or CD and either plain water or metformin (2.5 mg/mL in drinking water). Dams were euthanized on day e17.5 and fetal livers harvested and frozen at -80°C. RNA was extracted and hybridized to a customized 96-gene Nanostring panel focused on angiogenesis, inflammation, and growth gene expression. Fetal liver gene expression was compared between metformin and plain water groups using analysis of variance. Significant differences in gene expression, defined by a false discovery controlled q value <0.01, were then analyzed using Ingenuity pathway analysis (IPA). RESULTS: In HFD-fed dams, compared to controls, the metformin-treated group had significantly lower fetal weight and 39 differentially expressed liver genes; 15 (38%) were in the growth/angiogenesis gene expression network. IPA predicted that fetal liver gene upregulation associated with metformin exposure is a result of metformin inhibition of the common upstream regulator, phosphatase and tensin homolog ( PTEN). CONCLUSIONS: Metformin-exposed fetuses from dams fed HFD and CD have significant gene expression differences in genes specific to growth and angiogenesis pathways in the fetal liver. Diet alone did not alter fetal liver gene expression.

Maternal lipid levels during pregnancy and child weight status at 3 years of age.

BACKGROUND: The intrauterine environment is critical in the development of child obesity. OBJECTIVE: To investigate the association between maternal lipid levels during pregnancy and child weight status. METHODS: Maternal lipid levels (total cholesterol, high-density and low-density lipoprotein cholesterol, triglycerides) collected from fasting blood samples collected at less than 20 and 24-29 weeks' gestation and child weight status at age 3 were examined prospectively among 183 mother-child dyads enrolled in the Pregnancy, Infection, and Nutrition. Measured height and weight at 3 years were used to calculate age- and sex-specific body mass index z-scores. Child risk of overweight/obesity was defined as body mass index greater than or equal to 85th percentile for age and sex. Regression models estimated the association between maternal lipid levels and child body mass index z-score and risk of being affected by overweight/obesity, respectively. RESULTS: Higher triglyceride levels at less than 20 and 24-29 weeks of pregnancy were associated with higher body mass index z-scores (ß = 0.23; 95% CI: 0.07-0.38 and ß = 0.15; 95% CI: 0.01-0.29; respectively) after adjusting for confounders. There was no evidence of an association between total or low-density lipoprotein cholesterol and child weight status at age 3. CONCLUSIONS: Early childhood body mass index may be influenced by maternal triglyceride levels during pregnancy.