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OBJECTIVE:  The aim of Placental Assessment in Response to Environmental Pollution Study (PARENTs) was to determine whether imaging of the placenta by novel multiparametric magnetic resonance imaging (MRI) techniques in early pregnancy could help predict adverse pregnancy outcomes (APOs) due to ischemic placental disease (IPD). Additionally, we sought to determine maternal characteristics and environmental risk factors that contribute to IPD and secondary APOs. STUDY DESIGN:  Potential patients in their first trimester of pregnancy, who agreed to MRI of the placenta and measures of assessment of environmental pollution, were recruited into PARENTs, a prospective population-based cohort study. Participants were seen at three study visits during pregnancy and again at their delivery from 2015 to 2019. We collected data from interviews, chart abstractions, and imaging. Maternal biospecimens (serum, plasma, and urine) at antepartum study visits and delivery specimens (placenta, cord, and maternal blood) were collected, processed, and stored. The primary outcome was a composite of IPD, which included any of the following: placental abruption, hypertensive disease of pregnancy, fetal growth restriction, or a newborn of small for gestational age. RESULTS:  In this pilot cohort, of the 190 patients who completed pregnancy to viable delivery, 50 (26%) developed IPD. Among demographic characteristics, having a history of prior IPD in multiparous women was associated with the development of IPD. In the multiple novel perfusion measurements taken of the in vivo placenta using MRI, decreased high placental blood flow (mL/100 g/min) in early pregnancy (between 14 and 16 weeks) was found to be significantly associated with the later development of IPD. CONCLUSION:  Successful recruitment of the PARENTs prospective cohort demonstrated the feasibility and acceptability of the use of MRI in human pregnancy to study the placenta in vivo and at the same time collect environmental exposure data. Analysis is ongoing and we hope these methods will assist researchers in the design of prospective imaging studies of pregnancy. KEY POINTS: · MRI was acceptable and feasible for the study of the human placenta in vivo.. · Functional imaging of the placenta by MRI showed a significant decrease in high placental blood flow.. · Measures of environmental exposures are further being analyzed to predict IPD..

Objective This study aimed to test the hypothesis that being pregnant and delivering during the coronavirus disease 2019 (COVID-19) pandemic was associated with changes in gestational weight gain (GWG) or frequency of small- (SGA) or large-for-gestational-age (LGA) neonates. Study Design Secondary analysis of a multicenter observational cohort comparing pregnant people who delivered during the COVID-19 pandemic (June–December 2020) to people who delivered prior to the pandemic (March–December 2019). Those with multiple gestations, fetuses with major congenital anomalies, implausible GWG values, unavailable body mass index (BMI), or who were severe acute respiratory syndrome coronavirus-2-positive were excluded. The primary outcome was frequency of optimal recommended GWG based on prepregnancy BMI. Neonatal outcomes included birth weight, ponderal index, and frequency of SGA, LGA, and small head circumference for live births. Multivariable regression analysis was used to assess associations between exposure to the pandemic and outcomes. Results A total of 10,717 pregnant people were included in our analysis. A total of 4,225 pregnant people were exposed to the pandemic and 6,492 pregnant people delivered prior to the COVID-19 pandemic. Pregnant people exposed to the pandemic were older and more likely to have gestational diabetes. The frequency of appropriate GWG was 28.0% during the pandemic and 27.6% before the pandemic (adjusted odds ratio [aOR]: 1.02, 95% confidence interval [CI]: 0.93–1.11). Excessive GWG was more likely (54.9 vs. 53.1%; aOR: 1.08, 95% CI: 1.001–1.17), and inadequate GWG was less likely during the pandemic (17.0 vs. 19.3%; aOR: 0.86, 95% CI: 0.77–0.95). The frequency of SGA was 5.4% during the pandemic and 6.1% before the pandemic (aOR: 0.90, 95% CI: 0.76–1.06), and the frequency of LGA was 16.0% during the pandemic versus 15.0% before the pandemic (aOR: 1.06, 95% CI: 0.95–1.18). Other neonatal outcomes including birth weight percentile (62.1 [35.8–83.2] vs. 60.2 [34.4–82.2]; adjusted mean difference (aMD) = 1.50, 95% CI: −0.28 to 3.29), ponderal index (2.6 g/cm 3 [2.4–2.8] in both groups; aMD = 0.01, 95% CI: 0.00–0.02), and small head circumference for livebirths (<10th percentile [8.2 vs. 8.1%; aOR: 1.03, 95% CI: 0.89–1.19], <3rd percentile [3.5 vs. 3.1%; aOR: 1.16, 95% CI: 0.93–1.44]) were similar between groups as well. Conclusion Being pregnant and delivering during the COVID-19 pandemic was associated with a higher likelihood of excessive GWG and a lower likelihood of inadequate GWG. Key Points Delivering during the COVID-19 pandemic was associated with higher likelihood of excessive GWG. Delivering during the COVID-19 pandemic was associated with lower likelihood of inadequate GWG. COVID-19 pandemic was not associated with changes in frequency of SGA or LGA. [ABSTRACT FROM AUTHOR]

Objective We aimed to investigate the relationship between admission hypothermia and outcomes among very preterm infants (VPIs) in neonatal intensive care units (NICUs) in China. We also investigated the frequency of hypothermia in VPIs in China and the variation in hypothermia across Chinese Neonatal Network (CHNN) sites. Study Design This retrospective cohort study enrolled infants with 24 0/7 to 31 6/7 weeks of gestation with an admission body temperature ≤37.5 °C who were admitted to CHNN-participating NICUs between January 1 and December 31, 2019. Results A total of 5,913 VPIs were included in this study, of which 4,075 (68.9%) had hypothermia (<36.5 °C) at admission. The incidence of admission hypothermia varied widely across CHNN sites (9–100%). Lower gestational age (GA), lower birth weight, antenatal steroid administration, multiple births, small for GA, Apgar scores <7 at the 5th minute, and intensive resuscitation were significantly associated with admission hypothermia. Compared with infants with normothermia (36.5–37.5 °C), the adjusted odds ratios (ORs) for composite outcome among infants with admission hypothermia <35.5 °C increased to 1.47 (95% confidence interval [CI], 1.15–1.88). The adjusted ORs for mortality among infants with admission hypothermia (36.0–36.4 and <35.5 °C) increased to 1.41 (95% CI, 1.09–1.83) and 1.93 (95% CI, 1.31–2.85), respectively. Admission hypothermia was associated with a higher likelihood of bronchopulmonary dysplasia, but was not associated with necrotizing enterocolitis ≥stage II, severe intraventricular hemorrhage, cystic periventricular leukomalacia, severe retinopathy of prematurity, or sepsis. Conclusion Admission hypothermia remains a common problem for VPIs in a large cohort in China and is associated with adverse outcomes. Continuous quality improvement of admission hypothermia in the future may result in a substantial improvement in the outcomes of VPIs in China. Key Points Admission hypothermia is common in VPIs. The incidence of admission hypothermia in VPIs remains high in China. Admission hypothermia is associated with adverse outcomes in VPIs. [ABSTRACT FROM AUTHOR]

Objective Error in birthweight prediction by sonographic estimated fetal weight (EFW) has clinical implications, such as avoidable cesarean or misclassification of fetal risk in labor. We aimed to evaluate optimal timing of ultrasound and which fetal measurements contribute to error in fetal ultrasound estimations of birth size at the extremes of birthweight. Study Design We compared differences in head circumference (HC), abdominal circumference (AC), femur length, and EFW between ultrasound and corresponding birth measurements within 14 (n = 1,290) and 7 (n = 617) days of birth for small- (SGA, <10th percentile), appropriate- (AGA, 10th–90th), and large-for-gestational age (LGA, >90th) newborns. Results Average differences between EFW and birthweight for SGA neonates were: −40.2 g (confidence interval [CI]: −82.1, 1.6) at 14 days versus 13.6 g (CI: −52.4, 79.7) at 7 days; for AGA, −122.4 g (−139.6, −105.1) at 14 days versus −27.2 g (−50.4, −4.0) at 7 days; and for LGA, −242.8 g (−306.5, −179.1) at 14 days versus −72.1 g (−152.0, 7.9) at 7 days. Differences between fetal and neonatal HC were larger at 14 versus 7 days, and similar to patterns for EFW and birthweight, differences were the largest for LGA at both intervals. In contrast, differences between fetal and neonatal AC were larger at 7 versus 14 days, suggesting larger error in AC estimation closer to birth. Conclusion Using a standardized ultrasound protocol, SGA neonates had ultrasound measurements closer to actual birth measurements compared with AGA or LGA neonates. LGA neonates had the largest differences between fetal and neonatal size, with measurements 14 days from delivery showing 3- to 4-fold greater differences from birthweight. Differences in EFW and birthweight may not be explained by a single fetal measurement; whether estimation may be improved by incorporation of other knowable factors should be evaluated in future research. Key Points Ultrasound measurements may be inadequate to predict neonatal size at birth. Birthweight estimation error is higher for neonates >90th percentile. There is higher error in AC closer to birth. [ABSTRACT FROM AUTHOR]

Objective Our objective was to describe infant mortality within 1 year of life according to gestational age and birth weight percentile in infants delivered between 22 and 28 weeks of gestation. Study Design This study was a retrospective cohort study based on publicly available U.S. birth certificate data linked to infant death data between 2014 and 2020. Maternal–neonate pairs of singleton live births between 22 0/7 and 28 6/7 weeks' gestation (vaginal or cesarean) were evaluated. We excluded infants with major fetal anomalies, chromosomal disorders, and birth weight outliers. Our primary outcome was infant mortality within 1 year of life. Individuals were categorized into eight sex-specific birth weight percentiles categories: less than the 3rd, 3rd-less than the 10th, 10th-less than the 25th, 25th-to less than the 50th, 50th-less than the 75th, 75th-to less than the 90th, 90th-less than the 97th, and 97th or higher. Results Of 27,014,444 individuals with live births from January 2014 to December 2020, 151,677 individuals who gave birth at 22 to 28 weeks of gestation were included in the study population. The mortality rate ranged from 4.2% for the 50th-less than the 75th percentiles at 28 weeks to 80.3% for the 3rd-less than the 10th percentile at 22 weeks. Using the 50th-less than the 75th birth weight percentile at each gestational age as a reference group, birth weight less than the 50th percentile was associated with increased mortality at all gestational ages in a dose-dependent manner. From 22 to 25 weeks of gestation, higher birth weight percentiles were associated with lower mortality, while the 97th or higher birth weight percentile was associated with increased mortality compared with the 50th-less than the 75th birth weight percentile at 26 to 28 weeks of gestation. Conclusion The lower birth weight percentiles were associated with higher mortality across all gestational ages, but the association between higher birth weight percentiles and infant mortality exhibited an opposite pattern at 22 to 25 weeks as compared to later gestational age. Key Points Birth weight ≥97th percentile was associated with increased infant mortality at 26 to 28 weeks. Higher birth weight percentiles were associated with a lower risk of mortality at 22 to 25 weeks. Lower birth weight percentiles were associated with a higher risk of mortality at 22 to 28 weeks. [ABSTRACT FROM AUTHOR]

Objective Administering surfactant timely and appropriately is important to minimize lung injury but remains challenging in preterm neonates with respiratory distress syndrome. The published literature supports that lung ultrasound (LUS) score can predict surfactant need. Neonatal LUS scanning specification and parameter setting guidelines have been recently published for standardization. However, variations in scanning protocols and machine settings hinder its clinical implementation widely. This observational study aims to internally validate the suggested LUS protocol in a neonatal intensive care unit to establish a correlation between LUS scores and surfactant need as the first step of integrating LUS in the clinical practice. Study Design LUS was performed on 40 eligible preterm neonates within 3 hours after birth or before surfactant administration between May 2020 and March 2021. The neonates were between 27 and 32 weeks' gestational age, and all had respiratory distress. Neonates with known congenital anomalies were excluded. A high-frequency linear probe was used to obtain LUS images from six lung zones which were scored using a 0 to 3 system, yielding a maximum of 18 points. Treating physicians were blinded to the LUS score. Receiver operating characteristic analysis determined the optimal LUS score cut-off for predicting surfactant need. Results Fifteen of the 40 neonates (38%) required higher oxygen fraction and received surfactant. In our cohort, an LUS score ≥10 was identified as the optimal cut-off for predicting surfactant need, with a sensitivity of 80% and specificity of 84%. The area under the curve was 0.8 (p = 0.0003). LUS predicted surfactant need at a median of 3.5 hours earlier than traditional clinical decision (p < 0.0037). Conclusion LUS is a helpful adjunct for predicting surfactant need in preterm neonates. This study describes an approach to implement the LUS protocol and score for clinical decision-making in the clinical practice. Key Points LUS is a helpful adjunct for predicting surfactant need in preterm neonates. Machine setting variation and probe selection may affect LUS image and score. LUS score should be validated at the local unit before clinical implementation. [ABSTRACT FROM AUTHOR]

Objective The safety of weight loss and low weight gain during pregnancy remains unclear. To determine how different patterns of gestational weight gain (GWG), including weight loss, stability, and low GWG relate to perinatal outcomes by prepregnancy obesity class. Study Design The study population included 29,408 singleton livebirths among pregnant people with obesity from Kaiser Permanente Northern California (2008–2013). Clinically measured GWG was grouped into meaningful categories (Adequate: reference, met 2009 National Academy of Medicine [NAM] Guidelines [5–9.1 kg], Excessive [>9.1 kg], Low [1–4.9 kg], Stable [±1 kg], Weight Loss [>1 kg]) or GWG Z-score quintiles. Modified Poisson regression was used to estimate risk of adverse outcomes, stratified by obesity class. Electronic health record data were used to define outcomes, including cesarean delivery, preterm birth, admission to the neonatal intensive care unit, small- and large-for-gestational age infants. Results Prevalence of weight stability and weight loss was 3.8 and 3.4%, respectively. Compared with those who gained within NAM, increased risk of small-for-gestational age was observed among those with weight loss among obesity class I (Risk Ratio (RR): 1.57, 95% confidence interval [CI]: 1.12, 2.19), obesity class II (RR: 2.18, 95% CI: 1.52, 3.13), and obesity class III (RR: 1.72, 95% CI: 1.21, 2.45). Weight loss was associated with a decreased risk of cesarean delivery among obesity class III, compared with NAM. Conclusion Weight loss during pregnancy is associated with increased risk of small-for-gestational age among all obesity classes, but not other adverse perinatal outcomes and may reduce risk of cesarean delivery. Low weight gain and weight stability are not associated with risk of adverse outcomes among those with class III obesity. GWG guidelines may need to vary by obesity class. Key Points Weight loss during pregnancy is associated with increased risk of small-for-gestational age among all obesity classes; but weight loss was not associated with other adverse perinatal outcomes. Among class III, low weight gain and weight stability are not associated with adverse perinatal outcomes. GWG guidelines may need to vary by obesity class. [ABSTRACT FROM AUTHOR]

Objective Necrotizing enterocolitis (NEC) primarily affects preterm, especially small for gestational age (SGA), infants. This study was designed to (1) describe frequency and timing of NEC in SGA versus non-SGA infants and (2) assess whether NEC is independently associated with the severity of intrauterine growth failure. Study Design Retrospective cohort study of infants without severe congenital malformations born <33 weeks' gestational age (GA) carried out from 2009 to 2021. The frequency and time of NEC were compared between SGA and non-SGA infants. Multivariate logistic regression was used to assess whether NEC was independently associated with intrauterine growth restriction. Severe growth restriction was defined as birth weight Z -score < −2. Results Among 2,940 infants, the frequency of NEC was higher in SGA than in non-SGA infants (25/268 [9.3%] vs. 110/2,672 [4.1%], respectively, p < 0.001). NEC developed 2 weeks later in SGA than non-SGA infants. In multivariate analysis, the adjusted odds of NEC increased with extreme prematurity (<28 weeks' GA) and with severe but not moderate growth restriction. The adjusted odds of NEC increased with urinary tract infection or sepsis within a week prior to NEC, were lower in infants fed their mother's own milk until discharge, and did not change over five epochs. NEC was independently associated with antenatal steroid (ANS) exposure in infants with birth weight (BW) Z -score < 0. Conclusion NEC was more frequent in SGA than in non-SGA infants and developed 2 weeks later in SGA infants. NEC was independently associated with severe intrauterine growth failure and with ANS exposure in infants with BW Z -score < 0. Key Points We studied 2,940 infants <33 weeks' GA. We assessed NEC. NEC was more frequent in SGA infants. NEC occurred 2 weeks later in SGA infants. NEC was associated with severe growth restriction. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to derive profiles of alcohol, tobacco, and recreational drug use during pregnancy for first-time mothers with latent class growth analysis (LCGA) and determine the association of these classes with the risk of adverse pregnancy outcomes (APO). Study Design A secondary analysis of a prospective cohort of Nulliparous Outcomes in Pregnancy: Monitoring Mothers-to-Be was conducted in eight medical centers across the United States from September 30, 2010, to September 23, 2013. Self-reported use of any alcohol, tobacco, or recreational drugs in the 1 month prior to the visit was assessed at up to four visits throughout pregnancy, and APOs included a composite of preterm birth, hypertensive disorder of pregnancy (HDP), small for gestational age (SGA) infant, or stillbirth, and each adverse outcome separately. Results Four latent classes were identified from the LCGA for 10,031 nulliparous pregnant women that were on average 26.9 years old (standard deviation [SD] = 5.7) and mostly non-Hispanic White (59.7%). Classes included consistent tobacco users (N = 517, 5.2%), nonusers (N = 8,945, 89.2%), alcohol users (N = 500, 5.0%), and a combination of alcohol/tobacco/drug users (N = 69, 0.7%). Logistic regression demonstrated that the class of tobacco users was more likely to have an APO (odds ratio [OR] = 1.48, 95% confidence interval [CI] = 1.22–1.81), preterm birth (OR = 1.53, 95% CI = 1.15–2.02), and SGA (OR = 1.79, 95% CI = 1.36–2.35) relative to the class of nonusers. The class of alcohol users was more likely to have HDP (OR = 1.37, 95% CI = 1.11–1.70) and less likely to have preterm birth (OR = 0.59, 95% CI = 0.38–0.90) and SGA (OR = 0.61, 95% CI = 0.40–0.93) compared to nonusers. Conclusion Trajectories of substance use are associated with APOs; thus, interventions to mitigate the use when encountered early in pregnancy are warranted. Key Points Four classes of substance use were identified. Tobacco users were at a higher risk of APO and alcohol users were at higher risk of HDP. Mitigation strategies are warranted to reduce APO. [ABSTRACT FROM AUTHOR]

Objective A ventricle-to-brain index (VBI) >0.35 is associated with low scores on the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) in preterm infants with birth weight <1,250 g. However, VBI obtained at the third ventricle has only moderate interobserver reliability. The objective of this study was to test (1) reliability of VBI measured at the foramen of Monro on the latest ultrasonogram (US) before discharge using the intraclass correlation coefficient (ICC) and (2) the relationship between VBI and BSID-III scores at ≥18 months corrected age. Study Design The present study is a single-center retrospective cohort study. Results The study included 270 preterm infants born at 23 0/7 to 28 6/7 weeks of gestational age. The ICC of VBI between independent measurements by two study radiologists on the first 50 patients was 0.934. Factors associated with the value of VBI included severe intraventricular hemorrhage, bronchopulmonary dysplasia, and systemic steroid administration for BPD but not postmenstrual age. In multivariate analysis, VBI was negatively and independently associated with cognitive (p = 0.002), language (p = 0.004), and motor (p < 0.001) BSID-III scores. The association between VBI and BSID-III scores was observed even in infants in whom the latest US was obtained before term equivalent age. The association between VBI and BSID-III scores was also observed after excluding those with severe intraventricular hemorrhage. Conclusion In this very preterm cohort the measurement of VBI had excellent reliability. Moreover, VBI measurements were negatively associated with motor, language, and cognitive BSID-III scores. Key Points Mean values of VBI are stable with postmenstrual age. Values at the foramen of Monro are reliable and reproducible. VBI is negatively associated with Bayley scores. The association is observed even before term age. [ABSTRACT FROM AUTHOR]

Objective Fetal growth restriction (FGR) is defined as an estimated fetal weight (EFW) or abdominal circumference (AC) <10th percentile (%ile) for gestational age (GA). An EFW <3rd %ile for GA is considered severe FGR (sFGR). It remains unknown if fetuses with isolated AC <3rd %ile should be considered sFGR. Our primary objective was to assess composite neonatal outcomes in fetuses with an AC <3 rd %ile and overall EFW 3rd to 9th %ile compared with those with an EFW <3rd %ile. Study Design This retrospective cohort study was undertaken at a tertiary academic center from January 2016 to December 2021. Inclusion criteria were singleton fetuses with an EFW <3rd %ile (Group 1) or AC <3rd %ile with EFW 3rd to 9th %ile (Group 2) at 28 weeks' gestation or greater. Exclusion criteria were multiple gestations, presence of a major fetal anomaly, resolution of FGR, genetic syndrome, or infection. Composite neonatal outcome was defined by any of the following: neonatal intensive care unit admission >48 hours, necrotizing enterocolitis, sepsis, respiratory distress syndrome, mechanical ventilation, retinopathy of prematurity, seizures, intraventricular hemorrhage, stillbirth, or death before discharge. Small for gestational age (SGA) was defined as birth weight <10th %ile for GA. Results A total of 743 patients fulfilled our study criteria, with 489 in Group 1 and 254 in Group 2. The composite neonatal outcome occurred in 281 (57.5%) neonates in Group 1 and 53 (20.9%) in Group 2 (p < 0.01). The rates of SGA at birth were 94.9 and 75.6% for Group 1 and Group 2, respectively (OR 5.99, 95% confidence interval 3.65–9.82). Conclusion Although AC <3rd %ile with EFW 3rd to 9th %ile is associated with a lower frequency of SGA and neonatal morbidity than EFW <3 %ile, fetuses with AC <3 %ile still exhibited moderate rates of these adverse perinatal outcomes. Consideration should be given to inclusion of an AC <3rd %ile with EFW 3rd to 9th %ile as a criterion for sFGR. However, prospective studies comparing delivery at 37 versus 38 to 39 weeks' gestation are needed to ensure improved outcomes before widespread adaptation in clinical practice. Key Points The composite neonatal outcome occurred in 57.5% of fetuses with an overall EFW <3rd %ile and 20.9% of fetuses with an AC <3rd %ile but EFW 3rd to 9th %ile. Both groups demonstrated a high positive predictive value for SGA birth weight. Consideration should be given to inclusion of an AC <3rd %ile as a criterion for sFGR. [ABSTRACT FROM AUTHOR]

Objective Our objective was to determine whether maternal blood angiogenic factors in suspected-small-for-gestational-age (sSGA) fetuses can predict critical adverse perinatal outcomes (CAPO) and improve risk assessment. Methods Women with singleton pregnancies diagnosed with sSGA, between 24 and 35 6/7 weeks' gestation, were included. Clinical and sonographic comprehensive evaluations were performed at enrolment. Plasma angiogenic factors, soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF), were obtained at diagnosis. In parallel, three attending maternal-fetal-medicine specialists predicted the risk (1–5 scale) of these pregnancies to develop CAPO, based on the clinical presentation. CAPOs were defined as prolonged neonatal intensive care unit hospitalization, fetal or neonatal death, and major neonatal morbidity. Statistical analysis included sensitivity, specificity, positive and negative predictive values, and receiver-operating characteristic (ROC) curve analyses. Results Of the 79 cases included, 32 were complicated by CAPO (40.5%). In SGA fetuses with CAPO, the sFlt-1/PlGF ratio was higher (p < 0.001) and PlGF was lower (p < 0.001) as compared with uncomplicated pregnancies. The areas under the ROC curves for specialists were 0.913, 0.824, and 0.811 and for PlGF and sFlt-1/PlGF ratio 0.926 and 0.900, respectively. CAPO was more common in pregnancies with absent end-diastolic flow or reversed end-diastolic flow (AEDF or REDF) in the umbilical artery upon enrolment (91.6%). Yet, 65.6% of cases involving CAPO occurred in patients without AEDF or REDF, and 66.6% of these cases were not identified by one or more of the experts. The sFlt-1/PlGF ratio identified 92.9% of the experts' errors in this group and 100% of the errors in cases with AEDF or REDF. Conclusion Among sSGA pregnancies prior to 36 weeks' gestation, angiogenic factors testing can identify most cases later complicated with CAPO. Our data demonstrate for the first time that these markers can reduce clinician judgment errors. Incorporation of these measures into decision-making algorithms could potentially improve management, outcomes, and even health care costs. Key Points Angiogenic factors at diagnosis of sSGA can be used to predict CAPO. The sFlt-1/PlGF ratio can flag sSGA pregnancies at increased risk. The sFlt-1/PlGF ratio at admission of sSGA adds to clinical assessment. [ABSTRACT FROM AUTHOR]

Objective The International Liaison Committee on Resuscitation (ILCOR) 2015 gave a weak recommendation based on low certainty of evidence against routine endotracheal (ET) suctioning in non-vigorous (NV) neonates born through meconium-stained amniotic fluid (MSAF) and suggested for immediate resuscitation without direct laryngoscopy. A need for ongoing surveillance post policy change has been stressed upon. This study compared the outcomes of NV MSAF neonates before and after implementation of the ILCOR 2015 recommendation. Study Design This was a prospective cohort study of term NV MSAF neonates who underwent immediate resuscitation without ET suctioning (no ET group, July 2018 to June 2019, n = 276) compared with historical control who underwent routine ET suction (ET group, July 2015 to June 2016, n = 271). Results Baseline characteristics revealed statistically significant higher proportion of male gender and small for gestational age neonates in the prospective cohort. There was no significant difference in the incidence of primary outcome of meconium aspiration syndrome (MAS) between the groups (no ET group: 27.2% vs ET group: 25.1%; p = 0.57). NV MSAF neonates with hypoxic ischemic encephalopathy (HIE) was significantly lesser in the prospective cohort (no ET group: 19.2% vs ET group: 27.3%; p = 0.03). Incidence of air leaks and need for any respiratory support significantly increased after policy change. In NV MSAF neonates with MAS, need for mechanical ventilation (MV) (no ET group: 24% vs ET group: 39.7%; p = 0.04) and mortality (no ET group: 18.7% vs ET group: 33.8%; p = 0.04) were significantly lesser. Conclusion Current study from a developing country indicates that immediate resuscitation and no routine ET suctioning of NV MSAF may not be associated with increased risk of MAS and may be associated with decreased risk of HIE. Increased requirement of any respiratory support and air leak post policy change needs further deliberation. Decreased risk of MV and mortality among those with MAS was observed. Key Points Not performing ET suction in NV MSAF infants is not associated with increase in the incidence of MAS. Initiating immediate resuscitation without ET suctioning was associated with decreased risk of HIE but increased receipt of any respiratory support and air leak. Large multicentric trial is required to generate robust evidence. [ABSTRACT FROM AUTHOR]

Objective We compared differences in perinatal outcomes among rural and nonrural women, stratified by maternal race/ethnicity. We also examined differences between majority minority rural counties with majority White rural counties. Study Design We conducted a retrospective cohort study with 2015 national vital statistics birth certificate data. Maternal county of residence was identified, and counties with <50,000 people were designated as rural. We compared adverse perinatal outcomes between rural and nonrural residents, stratified by race/ethnicity. Adverse perinatal outcomes included primary term cesarean, preterm birth (PTB) <37 and <32 weeks, neonatal intensive care unit (NICU) admissions, infant death, small for gestational age, and Apgar's scores <7 and <3 at 5minutes. Majority–minority rural counties were defined as counties having <50% White women. We compared perinatal outcomes among this cohort to those of women from majority White rural counties. Bivariate analysis and multivariable logistic regression were performed. Results Within the entire cohort, rural residents were more likely to be younger (age ≥35 years, 10.1 vs. 16.8%; p <0.001), Medicaid beneficiaries (50.3 vs. 44.1%; p <0.001), and uninsured (6.6 vs. 4.2%; p <0.001), and less likely to be married (57.4 vs. 60.20%; p <0.001). Rural residence was associated with Apgar's score <7 (adjusted odds ratio [aOR]=2.04; 95% confidence interval [CI]: 1.64–2.54) and <3 (aOR=1.90; 95% CI: 1.04–3.48) among Asian women. Rural residence was also associated with PTB <37 weeks among Black (aOR=1.09; 95% CI: 1.06–1.13) and Asian women (aOR=1.16; 95% CI: 1.03–1.31). When compared with majority White rural county of residence, majority–minority rural county of residence was associated with the adverse perinatal outcomes studied. Conclusion We observed increased rates of adverse perinatal outcomes among rural women. These trends persisted in majority–minority rural. Additional study is needed to find actionable targets for improving outcomes for rural women. Key Points Rural county of residence was associated with lower socioeconomic markers. Perinatal outcomes were worse among women from rural counties. Differences in perinatal outcomes exist among rural women by race/ethnicity. [ABSTRACT FROM AUTHOR]

Objective Delta-like homolog 1 (DLK1) is a growth factor that is reduced in maternal sera in pregnancies with small for gestational age neonates. We sought to determine if DLK1 is associated with stillbirth (SB), with and without placental insufficiency. Study Design A nested case-control study was performed using maternal sera from a multicenter case-control study of SB and live birth (LB). SB and LB were stratified as placental insufficiency cases (small for gestational age <5% or circulatory lesions on placental histopathology) or normal placenta controls (appropriate for gestational age and no circulatory lesions). Enzyme-linked immunosorbent assay (ELISA) was used to measure DLK1. The mean difference in DLK1 was compared on the log scale in an adjusted linear regression model with pairwise differences, stratified by term/preterm deliveries among DLK1 results in the quantifiable range. In exploratory analysis, geometric means were compared among all data and the proportion of "low DLK1" (less than the median value for gestational age) was compared between groups and modeled using linear and logistic regression, respectively. Results Overall, 234 SB and 234 LB were analyzed; 246 DLK1 values were quantifiable within the standard curve. Pairwise comparisons of case and control DLK1 geometric means showed no significant differences between groups. In exploratory analysis of all data, adjusted analysis revealed a significant difference for the LB comparison only (SB: 71.9 vs. 99.1 pg/mL, p = 0.097; LB: 37.6 vs. 98.1 pg/mL, p = 0.005). In exploratory analysis of "low DLK1," there was a significant difference between the odds ratio of having "low DLK1" between preterm cases and controls for both SB and LB. There were no significant differences in geometric means nor "low DLK1" between SB and LB. Conclusion In exploratory analysis, more placental insufficiency cases in preterm SB and LB had "low DLK1." However, low DLK1 levels were not associated with SB. Key Points Maternally circulating DLK1 is correlated with placental insufficiency. Maternally circulating DLK1 is not correlated with SB. DLK1 is a promising marker for placental insufficiency. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to evaluate the diagnostic utility of serial growth ultrasounds for the indication of maternal overweight or obesity. Study Design This is a retrospective cohort study of all women with a body mass index ≥25 kg/m 2 who underwent at least one growth ultrasound at ≥24 weeks gestation and delivered at a single tertiary care institution between January 2010 and December 2013. Women were excluded if they had other medical indications for growth ultrasounds. Ultrasounds were divided into three gestational age epochs: 24 to 31 6/7 weeks, 32 to 35 6/7 weeks, and ≥36 weeks. Outcomes examined included the accuracy of sonographic detection of fetal growth restriction (FGR) and fetal overgrowth compared with diagnoses of small for gestational age (SGA) and large for gestational age (LGA) based on the birth weight. The test characteristics of ultrasound and the number needed to screen (NNS) to detect growth abnormalities at the time of birth were estimated for each condition and gestational age epoch. The NNS for the detection of fluid abnormalities was also assessed. Results During the study period, 3,945 eligible sonograms were performed in 2,928 women. FGR was identified on ultrasound in 42 (1.4%) women, fetal overgrowth in 94 (3.2%) women, oligohydramnios in 35 (1.2%) women, and hydramnios in 41 (1.4%) women. The NNS for the diagnoses of SGA, LGA, oligohydramnios, and hydramnios at delivery was at least 137 prior to 32 weeks of gestation and decreased (i.e., at least 45 and 16, for 32 to 35 6/7 weeks and ≥36 weeks, respectively) with advancing gestational age epochs. Conclusion If growth ultrasounds are to be performed for the sole indication of maternal overweight or obesity, consideration should be given to delaying initiation until at least 32 weeks of gestation given the infrequency of growth and fluid abnormalities identified earlier. Key Points There are limited data to support serial growth ultrasounds in overweight and obese women. The sensitivity of ultrasound for growth abnormalities at <32 weeks is low in women with BMI ≥25 Consideration should be given to delaying initiation of growth ultrasounds until at least 32 weeks [ABSTRACT FROM AUTHOR]

Objective Our objective was to summarize the literature regarding the effects of cannabis use during pregnancy on low birth weight (LBW), preterm birth (PTB), and small for gestational age (SGA). Study Design This is a systematic review and meta-analysis. A literature search was conducted in PubMed, Scopus, EBSCO, and Web of Science in May 2021 and updated in November 2021. Only studies that assessed the isolated use of cannabis during pregnancy, controlling for cigarette smoking, and other illicit drug use were included. Data were synthesized using a narrative summary and pooled adjusted estimates, and 95% confidence intervals (CIs) were calculated for each outcome. Data were analyzed using Stata 13.0 with METAN software package, using random effects. Statistical heterogeneity was assessed using Cochran's Q and Higgins I2 tests. Results In total, 32 studies were included with data from approximately 5.5 million women with the LBW outcome and 23 million with the PTB and SGA outcomes. Pregnant women using cannabis are at increased risk for LBW (adjusted odds ratio [aOR] = 1.52; 95% CI = [1.18; 1.96]), PTB (aOR = 1.39; 95% CI = [1.28; 1.51]), and SGA (aOR = 1.47; 95% CI = [1.38; 1.58]). Studies that assessed the type of PTB and gestational age at birth indicate higher risks of spontaneous PTB and of early or very-early PTBs associated with cannabis use during pregnancy. The few studies that assessed the timing and frequency of consumption suggest a dose–response effect, with higher odds of negative outcomes among women who reported heavy use and with continued use during the second and third trimesters of gestation. Conclusion There is an effect of cannabis irrespective of other illicit drugs and tobacco despite high heterogeneity and low quality of evidence. There is a need to discuss public policies regarding cannabis' regulation and how it influences its consumption. Future studies should focus on the effects of cannabis's type (medicinal or recreational), timing, and dosage during pregnancy on perinatal outcomes. Key Points Cannabis use during pregnancy is increasing. Cannabis has an independent effect on PTB, LBW, and SGA. Future studies should focus on the timing of exposure during pregnancy, mode of use, and dosage. [ABSTRACT FROM AUTHOR]

Objective To determine if women who newly met criteria for stage 1 hypertension in early pregnancy were at increased risk for adverse perinatal outcomes compared with normotensive women. Study Design We conducted a retrospective cohort study of women who had prenatal care at a single institution and subsequently delivered a live infant between December 2017 and August 2019. Women with a singleton gestation who had at least two prenatal visits prior to 20 weeks of gestation were included. We excluded women with known chronic hypertension or other major maternal illness. Two groups were identified: (1) women newly diagnosed with stage 1 hypertension before 20 weeks of gestation (blood pressure [BP]: 130–139/80–89 on at least two occasions) and (2) women with no known history of hypertension and normal BP (<130/80 mm Hg) before 20 weeks of gestation. The primary outcome was any hypertensive disorder of pregnancy; secondary outcomes were indicated preterm birth and small for gestational age. Generalized linear models were used to compare risk of adverse outcomes between the groups. Results Of the 1,630 women included in the analysis, 1,443 women were normotensive prior to 20 weeks of gestation and 187 women (11.5%) identified with stage 1 hypertension. Women with stage 1 hypertension were at significantly increased risk for any hypertensive disorder of pregnancy (adjusted risk ratio [aRR]: 1.86, 95% confidence interval [CI]: 1.12–3.04) and indicated preterm birth (aRR: 1.83, 95% CI: 1.12–3.02). Black women and obese women with stage 1 hypertension were at increased for hypertensive disorder of pregnancy compared with white women and nonobese women, respectively (aRR: 1.32, 95% CI: 1.11–1.57; aRR: 1.69, 95% CI: 1.39–2.06). Conclusion These results provide insight about the prevalence of stage 1 hypertension and inform future guidelines for diagnosis and management of hypertension in pregnancy. Future research is needed to assess potential interventions to mitigate risk. Key Points Stage 1 hypertension increased risk for hypertensive disorders of pregnancy and indicated preterm birth. Among women with stage 1 hypertension, risk of severe preeclampsia was 2.6 times higher than normotensive women. Black and obese women with stage 1 hypertension were at additional risk for adverse outcomes. [ABSTRACT FROM AUTHOR]

Objective This systematic review and meta-analysis (SRMA) aims to compare the efficacy of combining low molecular weight heparin (LMWH) and aspirin against aspirin alone in preventing preeclampsia (PE) and small for gestational age (SGA) neonates in women at moderate and high risks. Study Design The included studies were nonrandomized and randomized clinical trials (RCTs) enrolling women at moderate and high risks for developing preeclampsia. PubMed/Medline, Cochrane Library, Embase, and Grey literature (including ClinicalTrials.gov) were searched. Results Out of 4,762 records, 7 nonrandomized studies and 12 RCTs (enrolling 545 and 1,677 women, respectively) were selected. Although the studies were clinically heterogeneous, the conduction of quantitative analysis was feasible. Regarding RCTs, the odds of early-onset preeclampsia was reduced by 89% (pooled odds ratio [OR] = 0.11, 95% confidence interval [CI]: 0.01–0.93, p = 0.04) in women with thrombophilia, the incidence of SGA neonates below the 5th percentile by 48% (pooled OR = 0.52, 95% CI: 0.28–0.96, p = 0.04) in women with a history of preeclampsia and/or SGA neonates, and the incidence of SGA neonates below the 10th percentile by 31% (pooled OR = 0.69, 95% CI: 0.50–0.96, p = 0.03) in the whole population. Conclusion Concerning the whole studied population, combined anticoagulant therapy is not superior to aspirin alone. However, it may be more effective in preventing early-onset preeclampsia regarding women with thrombophilia, SGA neonates below the 5th percentile regarding women with a history of preeclampsia and/or SGA, and SGA neonates below the 10th percentile in moderate- or high-risk women. The above mixed but promising results need to be envisaged with caution due to the clinical heterogeneity of the included studies which is the main limitation of our research. Nevertheless, the strict and narrow inclusion search criteria, and the appropriate subgroup analysis are its main strengths. More RCTs with homogeneous populations and stricter inclusion criteria are needed to confirm these results. Key Points Combined therapy is not superior to aspirin alone. Combined therapy in women with thrombophilia may protect against early-onset preeclampsia. Combined therapy in moderate/high-risk women may protect against SGA <10th percentile neonates. [ABSTRACT FROM AUTHOR]

Objective Urinary tract infections are among the most common infections during pregnancy. The association between symptomatic lower urinary tract infections during pregnancy and fetal and maternal complications such as preterm birth and low birthweight remains unclear. The aim of this research is to evaluate the association between urinary tract infections during pregnancy and maternal and neonatal outcomes, especially preterm birth. Study Design This study is a secondary analysis of a multicenter prospective cohort study, which included patients between October 2011 and June 2013. The population consists of women with low risk singleton pregnancies. We divided the cohort into women with and without a symptomatic lower urinary tract infection after 20 weeks of gestation. Baseline characteristics and maternal and neonatal outcomes were compared between the two groups. Multivariable logistic regression analysis was used to correct for confounders. The main outcome was spontaneous preterm birth at <37 weeks. Results We identified 4,918 pregnant women eligible for enrollment, of whom 9.4% had a symptomatic lower urinary tract infection during their pregnancy. Women with symptomatic lower urinary tract infections were at increased risk for both preterm birth in general (12 vs. 5.1%, adjusted OR 2.5; 95% CI 1.7–3.5) as well as a spontaneous preterm birth at <37 weeks (8.2 vs. 3.7%, adjusted OR 2.3; 95% CI 1.5–3.5). This association was also present for early preterm birth at <34 weeks. Women with symptomatic lower urinary tract infections during pregnancy are also at increased risk of endometritis (8.9 vs. 1.8%, adjusted OR 5.3; 95% CI 1.4–20) and mastitis (7.8 vs. 1.8%, adjusted OR 4.0; 95% CI 1.6–10) postpartum. Conclusion Low risk women with symptomatic lower urinary tract infections during pregnancy are at increased risk of spontaneous preterm birth. In addition, an increased risk for endometritis and mastitis postpartum was found in women with symptomatic lower urinary tract infection during pregnancy. Key Points UTIs increase the risk of preterm birth. UTIs increase the risk of endometritis postpartum. UTIs increase the risk of mastitis postpartum. [ABSTRACT FROM AUTHOR]

Objective This study aimed to describe lethality of birth defects (BDs) in newborns categorized by gestational age and birth weight and to identify BDs associated with prematurity. Study Design Live born infants (n = 16,452) with isolated BDs classified by severity, and 42,511 healthy controls were assigned to categories: adequate growth, preterm, or small for gestational age (SGA). Proportion of cases and BDs' lethality rates were obtained by category and compared with controls. Results Overall fewer malformed than nonmalformed infants were of adequate growth, while the opposite occurred in the preterm and SGA categories where gastroschisis and esophageal atresia were among the most outstanding defects. For most severe BDs, the early neonatal death rate was higher than control values in all categories; for mild defects, except cleft lip in the preterm category, they did not differ. Diaphragmatic hernia showed the highest lethality values, while those of spina bifida were among the lowest. Talipes, hypospadias, and septal heart defects were mild defects significantly associated with prematurity. Conclusion Although reasons, such as induced preterm delivery of fetuses with certain anomalies, could partially account for their high prematurity rates, susceptibility to preterm birth might exist through underlying mechanisms related with the defects. The identification of BDs associated with prematurity should serve to improve measures that prevent preterm birth especially of fetuses at risk. Key Points Some BDs predispose to prematurity. Prematurity is an additional risk factor for mortality in infants with mild defects. Lethality values should be adjusted by gestational age and birth weight. [ABSTRACT FROM AUTHOR]

Objective This study was aimed to assess the association between ovarian hyperstimulation syndrome (OHSS) and pregnancy complications among women who conceived following fertility treatment. Study Design A retrospective population-based cohort study, including all singleton deliveries of patients conceived following ovulation induction (OI) or in vitro fertilization (IVF) between 1988 and 2016, was conducted. All births occurred in a single tertiary medical center. A comparison was performed between deliveries of women who had experienced OHSS at early gestation and subsequently had a pregnancy and women without OHSS. Women lacking prenatal care, multiple gestations, and stillbirths were excluded from the analyses. A multivariable logistic regression model was used to control for confounders. Results During the study period, 351,373 deliveries met the inclusion criteria, of which 6,748 were deliveries of infants who were conceived by either IVF or OI. Of this study population, 105 cases (1.6%) composed the exposed group, that is, women who had experienced OHSS with a subsequent live birth. In the multivariate analyses, after controlling for confounders, OHSS was not found as an independent risk factor for preeclampsia, gestational diabetes mellitus (GDM), intrauterine growth restriction (IUGR), preterm delivery (both <37 and <34 weeks), low birth weight (LBW), very LBW (VLBW), small for gestational age (SGA), and caesarean delivery. In a subanalysis conducted solely on the IVF population, similar results were found, aside from the association between OHSS and preterm delivery before 34 weeks of gestation which was statistically significant (adjusted odds ratio [AOR] = 2.3 95% confidence interval [CI]: 1.0–5.3, p = 0.049). Conclusion In our population, OHSS was not found as a risk factor for adverse pregnancy and perinatal outcome. In IVF patients, OHSS is a risk factor for preterm delivery before 34 weeks of gestation. Key Points OHSS is not a risk factor for pregnancy complications. Complications investigated were preeclampsia, GDM, prematurity, and others. In IVF patients, OHSS is a risk factor for preterm delivery. [ABSTRACT FROM AUTHOR]

Objective This study aimed to evaluate if early (within the first 3 hours after birth) transient neonatal hypoglycemia (TNH) is associated with poor academic performance in infants at-risk for hypoglycemia. Study Design This was a retrospective cohort study of at risk-infants (late preterm infants, small and large for gestational age infants, and infants of diabetic mothers [IDMs]) who were born in 1998 and 1999 at the University of Arkansas for Medical Sciences and had ≥1 recorded glucose concentration. The outcome measure was proficiency on 4th grade literacy and mathematics achievement tests. Three glucose concentration cutoffs for defining hypoglycemia (<35, <40, and <45 mg/dL) were investigated. Logistic regression models were developed to examine the association between early TNH and achievement test proficiency based on perinatal factors. Results Among 726 infants, 472 had one, 233 had two, and 21 had three risk factor(s). Early TNH (glucose concentration <35, <40, and <45 mg/dL) was observed in 6.3, 11.6, and 20.5% of the study cohort, respectively. Irrespective of the cutoff used, the frequency of early TNH (number of patients with early TNH in a risk category divided by the total number of patients in that category) was significantly greater among infants with multiple risk factors. After controlling for perinatal factors, early TNH (cutoffs <35 and <40 mg/dL) was significantly associated with decreased probability of proficiency in literacy but not mathematics. Despite that early TNH was more common in IDMs and infants with three risk factors, the category or number of risk factors did not impact academic proficiency. Conclusion Early TNH (<35 and <40 mg/dL) was associated with lower adjusted probability of proficiency on 4th grade literacy achievement tests in at-risk infants. The impact of early TNH on academic performance was similar irrespective of category or number of risk factors. Key Points Transient hypoglycemia was associated with lower proficiency on 4th grade tests in at-risk infants. The category of risk factors among at-risk infants did not impact 4th grade academic proficiency. The number of risk factors among at-risk infants did not impact 4th grade academic proficiency. [ABSTRACT FROM AUTHOR]

Objective The study aimed to analyze the risk factors and clinical features of metabolic bone disease of prematurity (MBDP) in premature infants compared with infants of similar gestational age and birth weight without MBDP. Study Design This retrospective case–control study was performed by comparing 81 cases of MBDP with 63 controls to identify potential risk factors. Premature infants with a gestational age ≤33 weeks and birth weight <1,500 g were included. Medical records were examined in terms of maternal conditions, potential risk factors, and clinical characteristics. Results Bone fractures and invasive ventilator dependence were the most common clinical features of MBDP. Duration of invasive ventilation and total mechanical ventilation days, necrotizing enterocolitis, corticosteroid use, anticonvulsive drug use, duration of dexamethasone and caffeine use, total parenteral nutrition, and length of hospitalization were significantly higher in neonates with MBDP (p < 0.05). Breastfed neonates and those receiving human milk fortifier had a lower incidence of MBDP than those premature formula or mixed feeding (p < 0.05). Anticonvulsive drug use (odds ratio: 2.935; 95% confidence interval: 1.265–6.810) was identified as a risk factor for MBDP at multiple regression analysis. Conclusion Our results show that anticonvulsive drug use is a significant risk factor for the development of MBDP. If long-term use is not required, anticonvulsive drugs should be stopped as soon as possible. Further studies involving patients with MBDP are required to determine the risk factors and clinical features. Key Points MBDP is a multifactorial disorder. Anticonvulsive drug use is an important risk factor for the development of MBDP. Bone fractures and invasive ventilator dependence are the most common clinical features of MBDP. [ABSTRACT FROM AUTHOR]

Objective The objective of the study was to determine whether adding longitudinal measures of fundal height (FH) to the standard cross-sectional FH to trigger third trimester ultrasound estimated fetal weight (EFW) would improve small for gestational age (SGA) prediction. Study Design We developed a longitudinal FH calculator in a secondary analysis of a prospective cohort study of 1,939 nonobese pregnant women who underwent serial FH evaluations at 12 U.S. clinical sites. We evaluated cross-sectional FH measurement ≤ –3 cm at visit 3 (mean: 32.0 ± 1.6 weeks) versus the addition of longitudinal FH up to and including visit 3 to trigger an ultrasound to diagnose SGA defined as birth weight <10th percentile. If the FH cut points were not met, the SGA screen was classified as negative. If FH cut points were met and EFW was <10th percentile, the SGA screen was considered positive. If EFW was ≥10th percentile, the SGA screen was also considered negative. Sensitivity, specificity, and positive predictive value (PPV) and negative predictive value (NPV) were computed. Results In a comparison of methods, 5.8% of women were classified as at risk of SGA by both cross-sectional and longitudinal classification methods; cross-sectional FH identified an additional 4.0%, and longitudinal fundal height identified a separate, additional 4.5%. Using cross-sectional FH as an ultrasound trigger, EFW had a PPV and NPV for SGA of 69 and 92%, respectively. After adding longitudinal FH, PPV increased to 74%, whereas NPV of 92% remained unchanged; however, the number of women who underwent triggered EFW decreased from 9.7 to 5.7%. Conclusion An innovative approach for calculating longitudinal FH to the standard cross-sectional FH improved identification of SGA birth weight, while simultaneously reducing the number of triggered ultrasounds. As an essentially free-of-charge screening test, our novel method has potential to decrease costs as well as perinatal morbidity and mortality (through better prediction of SGA). Key Points We have developed an innovative calculator for fundal height trajectory. Longitudinal fundal height improves detection of SGA. As a low cost screening test, the fundal height calculator may decrease costs and morbidity through better prediction of SGA. [ABSTRACT FROM AUTHOR]

Objective The study aimed to assess the association between intrauterine growth of preterm infants and energy and macronutrient contents in their mothers' milk. Study Design A historical cohort of mothers of preterm infants was assessed according to offspring's intrauterine growth. Fetal growth restriction (FGR) was defined as small-for-gestational age or appropriate for gestational age with fetal growth deceleration. During the first 4 weeks after delivery, the composition of daily pool samples of mothers' milk was measured by using a mid-infrared human milk analyzer. Explanatory models for milk energy, true protein, total carbohydrate, and fat contents were obtained by generalized additive mixed effects regression models. Results In total, 127 milk samples were analyzed from 73 mothers who delivered 92 neonates. Energy content was significantly higher in mothers with chronic hypertension (average: +6.28 kcal/dL; 95% confidence interval [CI]: 0.54–12.01; p = 0.034) and for extremely preterm compared with very preterm infants (average: +5.95 kcal/dL; 95% CI: 2.16–9.73; p = 0.003), and weakly associated with single pregnancies (average: +3.38 kcal/dL; 95% CI: 0.07–6.83; p = 0.057). True protein content was significantly higher in mothers with chronic hypertension (average: +0.91 g/dL; 95% CI: 0.63–1.19; p < 0.001) and with hypertension induced by pregnancy (average: +0.25 g/dL, 95% CI: 0.07–0.44; p = 0.007), and for extremely preterm compared with very and moderate preterm infants (average: +0.19; 95% CI: 0.01–0.38; p = 0.043 and +0.28 g/dL; 95% CI: 0.05–0.51; p = 0.017, respectively). Fat content was weakly and negatively associated with FGR, both in SGA infants and AGA infants with fetal growth deceleration (average: −0.44 g/dL; 95% CI: −0.92 to −0.05; p = 0.079 and average: −0.36 g/dL; 95% CI: −0.74 to −0.02; p = 0.066, respectively). Conclusion Energy and macronutrient contents in mothers' milk of preterm infants was significantly and positively associated with the degree of prematurity and hypertension. The hypothesis that the composition of milk is associated with FGR was not demonstrated. Key Points Energy and protein are higher for more immature infants. Energy and/or protein is higher in hypertension. Fat may be lower for infants with intrauterine growth restriction. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective There is wide variation in the management of pregnancies complicated by abnormal placental cord insertion (PCI), which includes velamentous cord insertion (VCI) and marginal cord insertion (MCI). We tested the hypothesis that abnormal PCI is associated with small for gestational age (SGA) infants. Study Design This is a retrospective cohort study of all pregnant patients undergoing anatomic ultrasound at a single institution from 2010 to 2017. Patients with abnormal PCI were matched in a 1:2 ratio by race, parity, gestational age at the time of ultrasound, and obesity to patients with normal PCIs. The primary outcome was SGA at delivery. Secondary outcomes were cesarean delivery, preterm delivery, cesarean delivery for nonreassuring fetal status, 5-minute Apgar score < 7, umbilical artery pH < 7.1, and neonatal intensive care unit admission. These outcomes were compared using univariate and bivariate analyses. Results Abnormal PCI was associated with an increased risk of SGA (relative risk [RR]: 2.43; 95% confidence interval [CI]: 1.26–4.69), increased risk of preterm delivery <37 weeks (RR: 3.60; 95% CI: 1.74–7.46), and <34 weeks (RR: 3.50; 95% CI: 1.05–11.63) compared with patients with normal PCI. There was no difference in rates of cesarean delivery, Apgar score of <7 at 5 minutes, acidemia, or neonatal intensive care unit admission between normal and abnormal PCI groups. In a stratified analysis, the association between abnormal PCI and SGA did not differ by the type of abnormal PCI (p for interaction = 0.46). Conclusion Abnormal PCI is associated with an increased risk of SGA and preterm delivery. These results suggest that serial fetal growth assessments in this population may be warranted. Key Points Abnormal PCI is associated with SGA infants and preterm birth. If an abnormal PCI is identified, the provider should consider serial growth ultrasounds. There is no difference in obstetric outcomes between VCI and MCI. [ABSTRACT FROM AUTHOR]

Objective  The aim of this study was to determine the association of prenatal marijuana exposure with and without tobacco smoke exposure and small for gestational age (SGA) at birth. Study Design  We conducted a secondary analysis of the prospective Lifestyle and Early Achievement in Families (LEAF) cohort enrolled from 2010 to 2015. We included singleton nonanomalous liveborn pregnancies. We assessed marijuana use inclusive of any pregnancy urine specimen with a Δ9-THC-COOH concentration of more than 15 ng/mL by mass spectrometry, self-report on questionnaire, and/or electronic health record; and self-reported maternal tobacco use. Because of the high co-frequency of marijuana with tobacco exposure in pregnancy and the known association between tobacco and fetal growth restriction, we modeled the exposure as: both marijuana and tobacco (hereafter "co-use"), only marijuana, only tobacco, and neither (reference). Incidence of SGA in each group was compared with the neither group. The primary outcome was SGA less than 10th percentile, and secondarily less than 5th percentile, using parity-specific definitions per 2017 US natality reference data. Results  Among 325 assessed mothers, 46% had neither exposure, 11% had only prenatal marijuana exposure, 20% only tobacco exposure, and 23% co-use exposure. A third (33%) of infants were SGA less than 10th percentile and 20% SGA less than 5th percentile. Marijuana exposure only was associated with an increased risk of SGA less than 10th percentile (43 vs. 26%; adjusted relative risk [aRR]: 1.66; 95% confidence interval [CI]: 1.02–2.69), and SGA less than5th percentile (30 vs. 13%; aRR: 2.26; 95% CI: 1.15–4.47). Tobacco was not associated with SGA less than 10th percentile, but was with SGA less than 5th percentile (26 vs. 13%; aRR: 2.01; 95% CI: 1.13, 3.56). Co-use was not associated with increased SGA risk in multivariate analysis, but was in sensitivity analysis when tobacco use was defined using a cotinine assay rather than self-report (SGA <10th percentile, aRR: 1.97; 95% CI: 1.24–3.15) and (SGA <5th percentile, aRR: 2.03; 95% CI: 1.09–3.78). Conclusion  Prenatal marijuana exposure in addition to tobacco may increase the risk of SGA. Given the rising prevalence of marijuana use in pregnancy, further research is warranted to understand how in utero marijuana exposure may impact fetal growth and birth weight with and without tobacco exposure. Key Points Marijuana and tobacco are commonly used together in pregnancy. Prenatal marijuana and tobacco exposure may increase the risk of a small for gestational age infant. Further research is warranted to understand how in utero marijuana exposure impacts fetal growth. [ABSTRACT FROM AUTHOR]

Objective  Fetal growth restriction (FGR) is associated with poor neonatal outcomes and stillbirth, and screening via fundal height or ultrasound is routinely performed. During the novel coronavirus disease 2019 (COVID-19) pandemic, we developed a hybrid model of prenatal care which decreased the frequency of in-person visits and incorporated telemedicine visits. We sought to determine if prenatal FGR diagnoses decreased with this hybrid model compared with routine prenatal care. Study Design  This was a retrospective cohort study of singleton nonanomalous neonates with birth weights <10th percentile at term. The "routine care" group was consisted of those who born between April and July 2019 with in-person prenatal care, and the "hybrid care" group was consisted of those who born between April and July 2020 with both in-person and telemedicine prenatal cares at a collaborative academic practice. The primary outcome was the rate of diagnosis of small for gestational age (SGA) as defined as infant birth weight <10th percentile without a prenatal diagnosis of FGR. The secondary outcome was timing of diagnosis of FGR. Results  Overall, 1,345 and 1,296 women gave birth in the routine and hybrid groups, respectively. The number of in-person prenatal care visits decreased from 15,024 in the routine period to 7,727 in the hybrid period; 3,265 telemedicine visits occurred during the hybrid period. The total number of prenatal patients remained relatively stable at 3,993 and 3,753 between periods. Third trimester ultrasounds decreased from 2,929 to 2,014 between periods. Birth weights <10 percentile occurred in 115 (8.6%) births during the routine period and 79 (6.1%) births during the hybrid period. Of 115, 44 (38.3%) cases were prenatally diagnosed with FGR in the routine versus 28 of 79 (35.4%) in the hybrid group (p  = 0.76). Median gestational age at diagnosis did not vary between groups (36 vs. 37 weeks, p  = 0.44). Conclusion  A hybrid prenatal care model did not alter the detection of FGR. Future efforts should further explore the benefits of incorporating telemedicine into prenatal care. Key Points Telemedicine visits can provide comprehensive prenatal care. FGR was diagnosed equally with hybrid versus routine prenatal care. FGR diagnosis was not delayed with hybrid care. [ABSTRACT FROM AUTHOR]

Objective  This study aimed to evaluate the impact of elevated early hemoglobin A1c (HbA1c) values on perinatal outcomes in patients without a diagnosis of diabetes or gestational diabetes. Study Design  This is a retrospective study of patients with a singleton pregnancy who underwent universal HbA1c screening in early pregnancy at an urban tertiary care center between December 1, 2016, and December 31, 2018. Patients with pregestational diabetes mellitus (DM) and gestational DM (GDM) were excluded from analysis. The exposure of interest was HbA1c of 5.7 to 6.4% as measured on routine prenatal bloodwork at or during 16 weeks' gestation. The following pregnancy outcomes were assessed: preterm delivery <37 weeks, hypertensive disorders of pregnancy, shoulder dystocia, macrosomia (birth weight >4,000 g), small or large for gestational age neonate, operative vaginal delivery, third- or fourth-degree lacerations, cesarean delivery, neonatal intensive care unit (NICU) admission, neonatal hypoglycemia, and neonatal hyperbilirubinemia. Multivariable regression was performed to assess the relationship between HbA1c and selected adverse outcomes while controlling for potential confounders Results  Of the 2,621 patients who met inclusion criteria, 334 (12.7%) had an elevated HbA1c of 5.7 to 6.4%. Patients with an elevated HbA1c were more likely to be older, Black, multiparous, publically insured, obese, or have chronic hypertension than patients with normal HbA1c values. In the unadjusted analysis, patients with an elevated HbA1c were less likely to deliver at term (84.7 vs. 92.4%, p  = 0.006), but more likely to undergo cesarean section (32.8 vs. 27.6%, p  = 0.038), develop hypertensive disorders of pregnancy (31.9 vs. 23.2%, p  = 0.001), or deliver a macrosomic infant (10.5 vs. 6.8%, p  = 0.016) than those with a normal A1c. After adjusting for race, body mass index, insurance status, nulliparity, and age, however, only the relationship between HbA1c and spontaneous preterm birth remained significant (adjusted odds ratio [aOR] = 1.76, 95% confidence interval [CI]: 1.01–3.07). Conclusion  In our urban population, an elevated early HbA1c was associated with spontaneous preterm birth in nondiabetic patients Key Points In nondiabetic patients, early pregnancy HbA1c was associated with selected adverse outcomes. Rates of preterm birth, pregnancy-induced hypertension, cesarean section, and macrosomia were higher in patients with an elevated HbA1c. The relationship between early pregnancy HbA1c and spontaneous preterm birth remained significant after adjustment. [ABSTRACT FROM AUTHOR]

Objective  We examined the effects of maternal hypertensive disorders of pregnancy (HDP) on the mortality and neurodevelopmental outcomes in preterm very low birth weight (VLBW) infants (BW ≤1,500 g) based on their intrauterine growth status and gestational age (GA). Study Design  We included singleton VLBW infants born at <32 weeks' gestation registered in the Neonatal Research Network Japan database. The composite outcomes including death, cerebral palsy (CP), and developmental delay (DD) at 3 years of age were retrospectively compared among three groups: appropriate for GA (AGA) infants of mothers with and without HDP (H-AGA and N-AGA) and small for GA (SGA) infants of mothers with HDP (H-SGA). The adjusted odds ratios (AOR) and 95% confidence intervals (CI) stratified by the groups of every two gestational weeks were calculated after adjusting for the center, year of birth, sex, maternal age, maternal diabetes, antenatal steroid use, clinical chorioamnionitis, premature rupture of membranes, non-life-threatening congenital anomalies, and GA. Results  Of 19,323 eligible infants, outcomes were evaluated in 10,192 infants: 683 were H-AGA, 1,719 were H-SGA, and 7,790 were N-AGA. Between H-AGA and N-AGA, no significant difference was observed in the risk for death, CP, or DD in any GA groups. H-AGA had a lower risk for death, CP, or DD than H-SGA in the 24 to 25 weeks group (AOR: 0.434, 95% CI: 0.202–0.930). The odds for death, CP, or DD of H-SGA against N-AGA were found to be higher in the 24 to 25 weeks (AOR: 2.558, 95% CI: 1.558–3.272) and 26 to 27 weeks (AOR: 1.898, 95% CI: 1.427–2.526) groups, but lower in the 30 to 31 weeks group (AOR: 0.518, 95% CI: 0.335–0.800). Conclusion  There was a lack of follow-up data; however, the outcomes of liveborn preterm VLBW infants of mothers with HDP depended on their intrauterine growth status and GA at birth. Key Points The effects of HDP on preterm low birth weight infants need to be further examined. The outcomes were not different between AGA infants with and without maternal HDP. The outcomes of SGA infants with maternal HDP were dependent on their GA. [ABSTRACT FROM AUTHOR]

Objective  Survival of preterm infants differs dramatically depending on birthplace. No previous studies have compared outcomes of preterm infants between low middle-income and high-income countries such as India and the United States. The purpose of this study is to evaluate differences in care practices, resources, mortality, and morbidities in preterm infants with birth weight 700 to 1,500 g between two major neonatal centers in these countries. Study Design  This is a retrospective cohort study with de-identified data from Fernandez Hospital (FH) in Hyderabad, India, and Texas Children's Hospital (TCH) in Houston, TX, for infants born January 2016 to December 2018, and weighing 700 to 1,500 g at birth. The primary outcome was death before hospital discharge. Results  Of 1,195 infants, 736 were admitted to FH and 459 were admitted to TCH. After controlling for differences in gestational age, small for gestational age, and antenatal corticosteroid use, TCH patients had lower mortality before hospital discharge (adjusted odds ratio [aOR] = 0.28, 95% confidence interval [CI]: 0.16–0.48, p  < 0.001) and more bronchopulmonary dysplasia (BPD; aOR = 2.2, 95% CI: 1.51–3.21, p  < 0.001). The composite outcome of death or BPD and death or any major morbidity (BPD or intraventricular hemorrhage grade II or more or periventricular leukomalacia grade II or more or retinopathy of prematurity requiring treatment) were not different. Conclusion  In this study, TCH infants had decreased odds of death before hospital discharge compared with FH but higher odds of BPD, which may be related to increased survival and differences in care practices. Key Points Few studies compared outcomes of premature infants between different high-income countries. There are no studies comparing preterm infants between low middle-income and high-income countries such as India and the United States. This study evaluated detailed comparison of care practices and infrastructure of NICUs in India and United states. [ABSTRACT FROM AUTHOR]

Objective  Maternal malnutrition with disturbed lipid metabolism during pregnancy may affect the fetal lipid profile. We aimed to detect the relation between maternal and neonatal serum lipid profile, as well as to detect the serum lipid profile difference between small for gestational age (SGA) infants and appropriate for gestational age (AGA) infants to disclose the impact of maternal malnutrition on birth weight. Study Design  A cross-sectional study was conducted on 150 pregnant women coming to the labor room. Before delivery, maternal serum levels of high-density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides (TGs), and total cholesterol were assessed, then after delivery, cord blood samples were taken for assessment of the neonatal lipid profile. Birth weights were measured, then the neonates were divided into SGA and AGA groups. Results  Serum levels of LDL, TGs, and total cholesterol in the SGA infants were lower than that in the AGA infants. A positive correlation between maternal and neonatal serum TGs levels was found. Besides, there was a positive correlation between birth weight and maternal serum levels of LDL, TGs, and total cholesterol. Conclusion  Maternal serum lipid profile could be an indicator of the neonatal serum lipid profile and birth weight. Key Points SGA neonates have lower levels of serum lipids compared to AGA neonates. There is a positive correlation between maternal and neonatal triglycerides. There is a positive correlation between birth weight and maternal serum lipids. [ABSTRACT FROM AUTHOR]

Objective  Urotensin II (U-II) is a potent vasoconstrictor peptide, and increased U-II levels are associated with atherosclerosis and hypertension in adults. Low birth weight (LBW) infants have higher risks of such diseases in the future. A small number of nephrons is one of possible mechanism underlying these risks in LBW infants, while vascular elasticity and cardiac function might be another important factor. The objective of this study is to evaluate U-II levels in preterm LBW infants at an early stage of life and determine perinatal factors associated with U-II levels. Study Design  The study population consisted of 57 preterm LBW infants (26 males and 31 females), including 49 appropriate for gestational age (AGA) and 8 small for gestational age (SGA) infants, born at a gestational age of ≤34 weeks with a mean birth weight of 1,589 g. Serum U-II levels were measured at term-equivalent age to evaluate perinatal factors related to serum U-II levels. Results  Preterm SGA infants had significantly higher serum U-II levels than preterm AGA infants at term-equivalent age (p  = 0.019). Serum U-II levels in preterm LBW infants at term-equivalent age were inversely correlated with birth weight standard deviation (SD) score in a simple regression analysis (r  =  − 0.395, p  = 0,002) and the correlation was maintained in the multiple regression analysis. Conclusion  Our results indicate that birth weight SD score might be associated with serum U-II levels in preterm LBW infants at term-equivalent age. Further studies are required to determine whether U-II levels at an early stage of life might influence the risk of atherosclerosis and hypertension. Key Points U-II is a potent vasoconstrictor. We evaluated serum U-II levels in preterm infants. Fetal growth is negatively related to serum U-II levels. [ABSTRACT FROM AUTHOR]

Objective  This study aimed to investigate the association between excess and less than recommended gestational weight gain (GWG) and adverse maternal and neonatal outcomes in women with pregestational and gestational diabetes. Study Design  We conducted a secondary analysis of the National Institute of Child Health and Human Development (NICHD) Consortium on Safe Labor (CSL) study. We included deliveries >23 weeks of nonanomalous singletons with either pregestational or gestational diabetes. The exposure was GWG greater than or less than compared with the U.S. Institute of Medicine recommendations for total pregnancy weight gain per prepregnancy body mass index. Consistent with the 2020 Delphi outcome for diabetes in pregnancy, maternal outcomes included cesarean delivery and preeclampsia and neonatal outcomes included small for gestational age (SGA), large for gestational age (LGA), macrosomia >4,000 g, preterm birth <37 weeks, stillbirth, and neonatal death. We modeled both absolute GWG and GWG z -scores, standardized for gestational duration. Multivariable logistic regression with generalized estimating equations was used, adjusting for age, race/ethnicity, parity, prior cesarean delivery, chronic hypertension, tobacco use, U.S. region, and delivery year. Results  Of 8,322 deliveries (n  = 8,087 women) complicated by pregestational or gestational diabetes, 47% were in excess, 27% were within, and 26% were less than GWG recommendations. Deliveries with excess absolute GWG were at higher adjusted odds of cesarean delivery, preeclampsia, LGA, and macrosomia, compared with those within recommendations. Similar results were observed when using standardized GWG z -scores, in addition to higher likelihood of preterm birth and neonatal death. Less than recommended GWG was associated with a lower likelihood of these adverse outcomes but higher SGA. Additionally, less GWG by z -score was associated with a lower likelihood of stillbirth. Conclusion  Excess GWG increases the risk of adverse maternal and neonatal outcomes for women with pregestational and gestational diabetes. Less GWG than recommended may decrease this risk. Key Points Understanding the impact of GWG modeled using both absolute and standardized measures is needed. Among pregnant women with diabetes, excess GWG was common and increased the risk of adverse outcomes and less than recommended GWG may decrease the risk of adverse outcomes, including stillbirth. Current recommendations may require revision for women with diabetes in pregnancy. [ABSTRACT FROM AUTHOR]

Objective  Breast cancer is one of the most frequently diagnosed cancers in pregnancy and is commonly treated with chemotherapy. To date, studies examining effects of chemotherapy during pregnancy on fetal growth have yielded conflicting results, and most are limited by small sample sizes or are nonspecific with respect to cytotoxic regimen or type of cancer treated. We sought to evaluate the effect of chemotherapy for breast cancer in pregnancy on birthweight and small for gestational age infants. Study Design  This is a retrospective cohort study of 74 women diagnosed with pathologically confirmed breast cancer during pregnancy between 1997 and 2018 at one of three academic medical centers, who had a singleton birth with known birthweight. Forty-nine received chemotherapy and 25 did not receive chemotherapy. Linear regression modeling was used to compare birthweight (by gestational age and sex-specific z -score) by chemotherapy exposure. Subanalyses of specific chemotherapy regimen and duration of chemotherapy exposure were also performed. Placental, neonatal, and maternal outcomes were also analyzed by chemotherapy exposure. Results  In the adjusted model, chemotherapy exposure was associated with lower birthweight (Δ z -score = −0.49, p  = 0.03), but similar rates of small for gestational age (defined as birthweight <10th percentile for gestational age) infants (8.2 vs. 8.0%, p  = 1.0; Fisher's exact test). Each additional week of chemotherapy (Δ z -score = −0.05, p  = 0.03) was associated with decreased birthweight, although no association was found with specific chemotherapy regimen. Chemotherapy exposure was associated with lower median placental weight percentile by gestational age (9th vs. 75th, p  < 0.05). Secondary maternal outcomes were similar between the group that did and did not receive chemotherapy. Conclusion  Chemotherapy for breast cancer in pregnancy in this cohort is associated with lower birthweight but no difference in the rate of small for gestational age infants. Key Points Chemotherapy for breast cancer in pregnancy is associated with decreased birthweight but similar rates of small for gestational age infants. Birthweight did not differ according to chemotherapy regimen. There is no difference in the rate of small for gestational age infants. [ABSTRACT FROM AUTHOR]

Objective  This study aimed to evaluate whether intrapartum fetal electrocardiogram (ECG) tracings with ST-elevation or depression occur more frequently in each stage of labor in small-for-gestational age (SGA) or large-for-gestational age (LGA), as compared with appropriate-for-gestational age (AGA) fetuses. Study Design  We conducted a secondary analysis of a large, multicenter trial in which laboring patients underwent fetal ECG waveform-analysis. We excluded participants with diabetes mellitus and major fetal anomalies. Birth weight was categorized as SGA (<10th percentile), LGA (>90th percentile), or AGA (10–90th percentile) by using a gender and race/ethnicity specific nomogram. In adjusted analyses, the frequency of ECG tracings with ST-depression or ST-elevation without depression was compared according to birthweight categories and labor stage. Results  Our study included 4,971 laboring patients in the first stage and 4,074 in the second stage. During the first stage of labor, there were no differences in the frequency of ST-depression in SGA fetuses compared with AGA fetuses (6.7 vs. 5.5%; adjusted odds ratio [aOR]: 1.41, 95% confidence interval [CI]: 0.93–2.13), or in ST-elevation without depression (35.8 vs. 34.1%; aOR: 1.17, 95% CI: 0.94–1.46). During the second stage, there were no differences in the frequency of ST-depression in SGA fetuses compared with AGA fetuses (1.6 vs. 2.0%; aOR: 0.69, 95% CI: 0.27–1.73), or in ST-elevation without depression (16.2 vs. 18.1%; aOR: 0.90, 95% CI: 0.67–1.22). During the first stage of labor, there were no differences in the frequency of ST-depression in LGA fetuses compared with AGA fetuses (6.3 vs. 5.5%; aOR: 0.97, 95% CI: 0.60–1.57), or in ST-elevation without depression (33.1 vs. 34.1%; aOR: 0.80, 95% CI: 0.62–1.03); during the second stage of labor, the frequency of ST-depression in LGA compared with AGA fetuses (2.5 vs. 2.0%, aOR: 1.36, 95% CI: 0.61–3.03), and in ST-elevation without depression (15.5 vs. 18.1%; aOR: 0.83, 95% CI: 0.58–1.18) were similar as well. Conclusion  The frequency of intrapartum fetal ECG tracings with ST-events is similar among SGA, AGA, and LGA fetuses. Key Points SGA and LGA neonates are at increased risk of cardiac dysfunction. Fetal ECG has been used to evaluate fetal response to hypoxia. Fetal ST-elevation and ST-depression occur during hypoxia. Frequency of intrapartum ST-events is similar among SGA, AGA and LGA fetuses. [ABSTRACT FROM AUTHOR]

Objective  This study aimed to examine the effects of interpregnancy weight change on pregnancy outcomes, including recurrent preeclampsia, preterm birth, small-for-gestational age (SGA), large-for-gestational age (LGA), and cesarean delivery, among women with a history of preeclampsia. We also evaluated whether these associations were modified by prepregnancy body mass index (BMI) category in the first pregnancy (BMI < 25 vs. ≥25 kg/m 2) and if associations were present among women who maintained a healthy BMI category in both pregnancies. Study Design  We conducted a population-based retrospective cohort study including 15,108 women who delivered their first two nonanomalous singleton live births in Missouri (1989–2005) and experienced preeclampsia in the first pregnancy. We performed Poisson regression with robust error variance to estimate relative risks and 95% confidence intervals for outcomes of interest after controlling for potential confounders. Results  Interpregnancy weight gain was associated with increased risk of recurrent preeclampsia, LGA, and cesarean delivery. These risks increased in a "dose–response" manner with increasing magnitude of interpregnancy weight gain and were generally more pronounced among women who were underweight or normal weight in the first pregnancy. Interpregnancy weight loss exceeding 1 BMI unit was associated with increased risk of SGA among underweight and normal weight women, while interpregnancy weight loss exceeding 2 BMI units was associated with reduced risk of recurrent preeclampsia among overweight and obese women. Conclusion  Even small changes in interpregnancy weight may significantly affect pregnancy outcomes among formerly preeclamptic women. Appropriate weight management between pregnancies has the potential to attenuate such risks. Key Points Interpregnancy weight change among formerly preeclamptic women significantly affects pregnancy outcomes. Interpregnancy weight gain is associated with increased risk of recurrent preeclampsia, large-for-gestational-age and cesarean delivery. Interpregnancy weight loss is associated with increased risk of small-for-gestational age and recurrent preeclampsia. [ABSTRACT FROM AUTHOR]

Objective  Our objective was to determine if the duration off respiratory support prior to discharge home from the neonatal intensive care unit (NICU) would impact hospital readmission rates among extremely low gestational age neonates (ELGAN). Study Design  In this retrospective chart review, we examined readmission rates for ELGAN admitted to the Montefiore–Weiler NICU between 2013 and 2015. Results  Of 140 infants born at <29 weeks' gestational age, 30 (21%) of these infants were subsequently readmitted within 90 days, primarily for respiratory complaints. Readmitted infants were born at an earlier gestational age (median = 26 weeks; interquartile range [IQR]: 24–27 weeks) compared to infants who did not require readmission (median = 27 weeks; IQR: 25-28 weeks), p  = 0.03. Birth weights were smaller among infants who required readmission, 800 ± 248 g compared to 910 ± 214 g (p  = 0.02). Infants with Hispanic ethnicity and those discharged during the spring season were likely to be readmitted. Duration off respiratory support prior to discharge did not predict 90-day readmission rates. Lower gestational age and birth weight were associated with higher rates of readmissions after NICU discharge. Conclusion  Duration off and invasiveness of respiratory support prior to discharge did not predict risk of 90-day readmission nor did discharge during months with traditionally higher prevalence of respiratory viruses. [ABSTRACT FROM AUTHOR]

Objective  The aim of the study is to compare maternal and neonatal outcomes among patients who are normotensive, hypertensive by Stage I American College of Cardiology-American Heart Association (ACC-AHA) criteria, and hypertensive by American College of Obstetricians and Gynecologists (ACOG) criteria. Study Design  Secondary analysis of a prospective first trimester cohort study between 2007 and 2010 at three institutions in Baltimore, MD, was conducted. Blood pressure at 11 to 14 weeks' gestation was classified as (1) normotensive (systolic blood pressure [SBP] <130 mm Hg and diastolic blood pressure [DBP] <80 mm Hg); (2) hypertensive by Stage I ACC-AHA criteria (SBP 130–139 mm Hg or DBP 80–89 mm Hg); or (3) hypertensive by ACOG criteria (SBP ≥140 mm Hg or DBP ≥90 mm Hg). Primary outcomes included preeclampsia, small for gestational age (SGA) neonate, and preterm birth. Results  Among 3,422 women enrolled, 2,976 with delivery data from singleton pregnancies of nonanomalous fetuses were included. In total, 20.2% met hypertension criteria (Stage I ACC-AHA n  = 254, 8.5%; ACOG n  = 347, 11.7%). The Stage I ACC-AHA group's risk for developing preeclampsia was threefold higher than the normotensive group (adjusted relative risk [aRR] 3.70, 95% confidence interval [CI] 2.40–5.70). The Stage I ACC-AHA group had lower preeclampsia risk than the ACOG group but the difference was not significant (aRR 0.87, 95% CI 0.55–1.37). The Stage I ACC-AHA group was more likely than the normotensive group to deliver preterm (aRR 1.44, 95% CI 1.02–2.01) and deliver an SGA neonate (aRR 1.51, 95% CI 1.07–2.12). The Stage I ACC-AHA group was less likely to deliver preterm compared with the ACOG group (aRR 0.65, 95% CI 0.45–0.93), but differences in SGA were not significant (aRR 1.31, 95% CI 0.84–2.03). Conclusion  Pregnant patients with Stage I ACC-AHA hypertension in the first trimester had higher rates of preeclampsia, preterm birth, and SGA neonates compared with normotensive women. Adverse maternal and neonatal outcomes were numerically lower in the Stage I ACC-AHA group compared with the ACOG group, but these comparisons only reached statistical significance for preterm birth. Optimal pregnancy management for first trimester Stage I ACC-AHA hypertension requires active study. Key Points Women with first trimester American College of Cardiology-American Heart Association (ACC-AHA) Stage I hypertension were more likely to develop preeclampsia, deliver preterm, and deliver a small-for-gestational age neonate than normotensive women. Women with first trimester American College of Obstetricians and Gynecologists (ACOG) hypertension (consistent with stage II ACC-AHA hypertension) had the highest numeric rate of adverse outcomes; however, compared with Stage I ACC-AHA hypertension, there was only statistically significant difference for preterm delivery. The risk profile for pregnant women with Stage I ACC-AHA hypertension and women with hypertension by conventional ACOG criteria may be more similar than previously understood. [ABSTRACT FROM AUTHOR]

Objective  The aim of the study is to describe the rates of neonatal death and severe neonatal morbidity in a contemporary cohort, as well as to evaluate the predictive value of birth gestational age (GA) and birth weight, independently and combined, for neonatal mortality and morbidity in the same contemporary cohort. Study Design  We performed a secondary analysis of an international, multicenter randomized controlled trial of delayed umbilical cord clamping versus umbilical cord milking in preterm infants born at 23 0/7 to 31 6/7 weeks of gestation. The current analysis was restricted to infants delivered <28 weeks. The primary outcomes of this analysis were neonatal death and a composite of severe neonatal morbidity. Incidence of outcomes was compared by weeks of GA, with planned subanalysis comparing small for gestational age (SGA) versus non-SGA neonates. Multivariable logistic regression was then used to model these outcomes based on birth GA, birth weight, or a combination of both as primary independent predictors to determine which had superior ability to predict outcomes. Results  Of 474 neonates in the original trial, 180 (38%) were included in this analysis. Overall, death occurred in 27 (15%) and severe morbidity in 139 (77%) neonates. Rates of mortality and morbidity declined with increasing GA (mortality 54% at 23 vs. 9% at 27 weeks). SGA infants (n  = 25) had significantly higher mortality compared with non-SGA infants across all GAs (p  < 0.01). There was no difference in the predictive value for neonatal death or severe morbidity between the three prediction options (GA, birth weight, or GA and birth weight). Conclusion  Death and severe neonatal morbidity declined with advancing GA, with higher rates of death in SGA infants. Birth GA and birth weight were both good predictors of outcomes; however, combining the two was not more predictive, even in SGA infants. Key Points We performed a secondary analysis of multicenter randomized clinical trials. The study included only extremely preterm neonates <28 weeks. We provide rates of neonatal morbidity in a contemporary cohort. [ABSTRACT FROM AUTHOR]

Objective  This study aims to estimate the association between abnormal placental histopathology, fetal growth restriction (FGR), and preeclampsia (PEC) in twin pregnancies. Study Design  Retrospective cohort study of women with diamniotic twin pregnancies with live births at ≥24 weeks of gestation and available placental pathology. Findings were compared between women with and without FGR, which was defined as a birthweight <10th percentile, using singleton and twin growth curves, and those with and without PEC. The primary study outcome was a composite of abnormal placental histopathology. Chi-square, Fisher's exact, and Student's t -tests were used for analysis. Results  Among 859 patients with diamniotic twins, 806 (93.8%) had placental pathology. A total of 422 (52.4%) women had at least one twin with FGR, using a singleton growth curve. FGR affected 136 (16.9%) pregnancies when a twin growth curve was applied. There was no significant difference in composite outcome between groups, using either growth curve (45.5 vs. 44.8%, p  = 0.84; adjusted odds ratio (aOR): 1.06, 95% CI: 0.79–1.40 and 52.2 vs. 43.7%, p  = 0.07; aOR: 1.44, 95% CI: 0.90–2.10). A total of 122 of 789 (15.5%) patients developed PEC. There was no significant difference in composite outcome between patients with and without PEC (41.8 vs. 45.4%, p  = 0.46; aOR: 0.79, 95% CI: 0.53–1.18). Conclusion  In twin pregnancies, FGR and PEC are not associated with abnormal placental histopathology. This suggests that the pathologic placental manifestations of these conditions may differ in twins and include factors other than those commonly described in singletons. [ABSTRACT FROM AUTHOR]

Objective  This study aimed to study the relationship between prenatal marijuana and infant birth weight using natural cohorts established before, during and after the 20-month lapse between legalization and legal recreational sales in Washington State. Study Design  Over 5 years, 5,343 pregnant women with documented urine drug screen (UDS) results delivered at Tacoma General Hospital or Good Samaritan Hospital. Maternal medical data were extracted for three delivery cohorts established based on before (T1), during (T2), and after legalization (T3) of recreational marijuana and legalized availability. Univariate and multivariate models were created to study marijuana exposure on infants' birth weight. Results  Marijuana exposure increased the risk of low birth weight (LBW; odds ratio [OR] = 1.42, 95% confidence interval [CI]: 1.01–2.01). This was more pronounced in full-term babies (OR = 1.72, 95% CI: 1.10–2.69), and was independently associated with a higher risk for small for gestational age (SGA; OR = 1.51, 95% CI: 1.49–1.53). The associations between marijuana exposure and SGA were maintained in cohort-specific models (OR = 1.53, 95% CI: 1.01–2.32 for T2, and OR = 1.43, 95% CI: 1.01–2.02 for T3, respectively). Conclusion  Marijuana exposure verified by UDS was associated with LBW and SGA. However, recreational marijuana legalization and availability did not have direct impact on newborns' risk of LBW or SGA. [ABSTRACT FROM AUTHOR]

Objective  This study aimed to determine associations between maternal cigarette smoking and adverse birth and maternal outcomes. Study Design  This is a 10-year population-based retrospective cohort study including 4,971,896 resident births in California. Pregnancy outcomes of maternal smokers were compared with those of nonsmokers. The outcomes of women who stopped smoking before or during various stages of pregnancy were also investigated. Results  Infants of women who smoked during pregnancy were twice as likely to have low birth weight (LBW) and be small for gestational age (SGA), 57% more likely to have very LBW (VLBW) or be a preterm birth (PTB), and 59% more likely to have a very PTB compared with infants of nonsmokers. During the study period, a significant widening of gaps developed in both rates of LBW and PTB and the percentage of SGA between infants of maternal smokers and nonsmokers. Conclusion  Smoking during pregnancy is associated with a significantly increased risk of adverse birth and maternal outcomes, and differences in rates of LBW, PTB, and SGA between infants of maternal smokers and nonsmokers increased during this period. Stopping smoking before pregnancy or even during the first trimester significantly decreased the infant risks of LBW, PTB, SGA, and the maternal risk for cesarean delivery. [ABSTRACT FROM AUTHOR]

Objectives  To identify whether advanced maternal age (AMA), defined as age ≥35 years old, is independently associated with small for gestational age (SGA). Study Design  This was a retrospective cohort of births from the National Vital Statistics System in the United States from 2009 to 2013. Women were categorized based on four age groups at the time of delivery: 20 to 29, 30 to 34, 35 to 39, and ≥40 years old. The primary outcome of SGA < 10th and SGA < 5th percentiles was compared between the four groups using both univariable and multivariable analyses to determine whether maternal age was associated with SGA independent of parity. Results  A total of 17,031,005 births were eligible for analysis, with 2,705,501 births to AMA women. In multivariable analyses, maternal age of 30 to 34, compared with 20 to 29, was associated with lower rates of SGA < 10th and <5th percentiles (adjusted odds ratio [aOR] = 0.95; 95% confidence interval [CI]: 0.95–0.96 and aOR = 0.97; 95% CI: 0.96–0.98, respectively). The AMA of 35 to 39, compared with 20 to 29, was associated with lower rates of SGA < 10th percentile and unchanged rates of SGA < 5th percentile (aOR = 0.97; 95% CI: 0.96–0.98 and aOR = 1; 95% CI: 0.99–1.01, respectively). In contrast, AMA of ≥40, compared with age 20 to 29, was associated with higher rates of both SGA < 10th and <5th percentiles (aOR = 1.06; 95% CI: 1.04–1.07 and aOR = 1.14; 95% CI: 1.12–1.16, respectively). A significant association was found between maternal age and parity toward the risk of SGA (p  < 0.001). Nulliparous women ≥30 years old but not multiparous women had higher rates of SGA < 10th and SGA < 5th percentiles compared with nulliparous women in the age group of 20 to 29. In contrast, both nulliparous and multiparous women age ≥40 years old had an increased risk for SGA < 5th percentile compared with all women in the age group of 20 to 29. Conclusion  Nulliparous women aged 30 years and older have higher risk of SGA < 10th and SGA < 5th percentiles compared with nulliparous women age 20 to 29. In contrast, both nulliparous and multiparous women age 40 years and older have an increased risk of SGA < 5th percentile compared with all women in the age group of 20 to 29. [ABSTRACT FROM AUTHOR]

Objective  Antibiotics are commonly used in pregnancy. Prior studies have indicated that antibiotic use in pregnancy may affect birth weight, whereas data in nonpregnant individuals suggest that antibiotic exposure may increase diabetes risk. We evaluated the impact of antibiotic prescriptions during pregnancy on the prevalence of small for gestational age (SGA) and large for gestational age (LGA) birth weight and gestational diabetes mellitus (GDM). Study Design  This retrospective cohort study of 12,551 women who delivered at a large academic medical center between 2012 and 2014 assessed the number and type of antibiotic prescriptions prior to GDM testing using the electronic medical record. SGA and LGA birth weight and GDM rates were compared among women who were or were not prescribed antibiotics. Results  Overall, 3,991 (31.8%) of 12,551 patients received at least one antibiotic prescription. After covariate adjustment, no differences existed in risk of SGA (adjusted odds ratio [aOR]: 1; 95% confidence interval [CI]: 0.88–1.15; p  = 0.94), LGA (aOR: 1; 95% CI: 0.86–1.17; p  = 0.97), or GDM (aOR: 0.90; 95% CI: 0.72–1.13; p  = 0.36) between women who were or were not prescribed antibiotics. Conclusion  Antibiotic use does not affect the risk of SGA or LGA birth weight or GDM in pregnant women. These results provide reassurance regarding the use of antibiotics when clinically indicated in pregnancy. [ABSTRACT FROM AUTHOR]

Objective Clinicians use estimated fetalweight (EFW) as a proxy for birth weight (BW) in the antenatal period. Our objective was to compare the accuracy of EFWobtained by ultrasound to BW among infants born during the periviable period and determine if accuracy of EFW varied among small for gestational age (SGA) versus appropriate for gestational age (AGA) grown neonates. Study Design We included women who delivered between 230/7 and 256/7 weeks' gestation and had an EFW within 7 days of delivery. Mean percentage difference and median absolute percentage difference between EFW and BW were calculated. Results Our cohort included 226 neonates with a mean gestational age of 241/7 ± 0.8 weeks and median BW of 653 g (interquartile range [IQR]: 580-750 g). The median absolute percentage difference between EFW and BW of fetal weight estimates was 9.2% (IQR: 3.6-17.2). EFW overestimated BW for 75% (n = 171) of the cohort. Among SGA infants, the mean percentage difference in EFW and BW was 16.2 ± 19.4% versus 6.9% ± 13.1% in AGA infants (p = 0.019). Conclusion EFW overestimated BW in this cohort. In addition, ultrasound was less accurate among infants born SGA. These data are important to consider when counseling families facing periviable delivery. [ABSTRACT FROM AUTHOR]

Objective To determine the effect of adopting sex or race/ethnicity-specific birthweight curves on small-for-gestational age (SGA)-associatedmortality rates for specific populations. Materials and Methods Analyzing 20,095,735 singleton pregnancies, we compared rates of perinatal death associated with SGA in distinct sex and racial/ethnic groups when SGA was defined using nonspecific, sex-specific, and race/ethnicity-specific birthweight curves. Results With use of a nonspecific birthweight curve, the rate of perinatal deathwas higher for SGA males (20.4/1,000 [95% confidence interval (CI), 20.1, 20.7]) than SGA females [14.6/1,000 (95% CI, 14.4, 14.8)]. With a sex-specific curve, this disparity was reduced, measuring 17.7/1,000 (95% CI, 17.4, 17.9) for SGA males and 16.3/1,000 (95% CI, 16.1, 16.6) for females. Using a nonspecific birthweight curve, perinatal death rates were higher for non-Hispanic blacks (20.4/1,000 [95% CI, 20.0, 20.8]) than for all other racial/ethnic groups (15.9/1,000 [95% CI, 15.7, 16.1]). This difference increased with use of a racespecific birthweight curve: perinatal mortality was 29.7/1,000 (95% CI, 29.0, 30.3) for SGA blacks and 14.7/1,000 (95% CI, 14.6, 14.9) for all other racial/ethnic groups. Conclusion Population-based differences in SGA-associated mortality are reduced with adoption of a sex-specific birthweight curve, but widen with use of a race/ ethnicity-specific curve. These findings highlight the importance of outcomes analysis in the selection of diagnostic criteria for SGA. [ABSTRACT FROM AUTHOR]

Objective This article aims to compare long-term neurodevelopmental and health outcomes of twins born at 34 weeks or later, based on the presence of small for gestational age (SGA). Study Design This study is a mail-based survey of twin gestations delivered by a single practice. We compared twins with and without SGA delivered at ≥34 weeks. There were two primary outcomes for this study: a composite of major adverse outcomes (death; cerebral palsy; necrotizing enterocolitis; chronic renal, heart, or lung disease) and a composite of minor adverse outcomes (learning disability, speech therapy, occupational therapy, physical therapy). Regression analysis was performed to control for clustering of outcomes within twin pairs. Results A total of 712 children were included. Comparing twins with birthweights <10% to ≥10%, there were no significant differences in rates of composite major morbidities (3.2 vs. 1.4%, p = 0.109) or composite minor morbidities (43.6 vs. 39.3%, p = 0.279). Comparing twins with birthweights <5% to ≥5%, the rates of major morbidities were low in both groups, but significantly higher in the group with birthweights <5% (4.4 vs. 1.6%, p = 0.046). There were no significant differences seen in the composite minor morbidities (46.7 vs. 39.7%, p = 0.134). Twins with birthweights <5% were significantly more likely to have childhood cardiac disease (2.9 vs. 0.7%, p = 0.041). Conclusion Twins with SGA <10% born at ≥34 weeks have similar long-term neurodevelopmental and health outcomes compared with twins with normal birth- weights. Birthweight less than 5th percentile is associated with an increased risk of major morbidity, specifically cardiac disease, but the absolute risk is low. [ABSTRACT FROM AUTHOR]