Fetal growth restriction and small for gestational age as predictors of neonatal morbidity: which growth nomogram to use?

BACKGROUND: Fetal growth nomograms were developed to screen for fetal growth restriction and guide clinical care to improve perinatal outcomes; however, existing literature remains inconclusive regarding which nomogram is the gold standard. OBJECTIVE: This study aimed to compare the ability of 4 commonly used nomograms (Hadlock, International Fetal and Newborn Growth Consortium for the 21st Century, Eunice Kennedy Shriver National Institute of Child Health and Human Development-unified standard, and World Health Organization fetal growth charts) and 1 institution-specific reference to predict small for gestational age and poor neonatal outcomes. STUDY DESIGN: This was a retrospective cohort study of all nonanomalous singleton pregnancies undergoing ultrasound at ≥20 weeks of gestation between 2013 and 2020 and delivering at a single academic center. Using random selection methods, the study sample was restricted to 1 pregnancy per patient and 1 ultrasound per pregnancy completed at ≥22 weeks of gestation. Fetal biometry data were used to calculate estimated fetal weight and percentiles according to the aforementioned 5 nomograms. Maternal and neonatal data were extracted from electronic medical records. Logistic regression was used to estimate the association between estimated fetal weight of <10th and <3rd percentiles compared with estimated fetal weight of 10th to 90th percentile as the reference group for small for gestational age and the neonatal composite outcomes (perinatal mortality, hypoxic-ischemic encephalopathy or seizures, respiratory morbidity, intraventricular hemorrhage, necrotizing enterocolitis, hyperbilirubinemia or hypoglycemia requiring neonatal intensive care unit admission, and retinopathy of prematurity). Receiver operating characteristic curve contrast estimation (primary analysis) and test characteristics were calculated for all nomograms and the prediction of small for gestational age and the neonatal composite outcomes. We restricted the sample to ultrasounds performed within 28 days of delivery; moreover, similar analyses were completed to assess the prediction of small for gestational age and neonatal composite outcomes. RESULTS: Among 10,045 participants, the proportion of fetuses classified as <10th percentile varied across nomograms from 4.9% to 9.7%. Fetuses with an estimated fetal weight of <10th percentile had an increased risk of small for gestational age (odds ratio, 9.9 [95% confidence interval, 8.5-11.5] to 12.8 [95% confidence interval, 10.9-15.0]). In addition, the estimated fetal weight of <10th and <3rd percentile was associated with increased risk of the neonatal composite outcome (odds ratio, 2.4 [95% confidence interval, 2.0-2.8] to 3.5 [95% confidence interval, 2.9-4.3] and 5.7 [95% confidence interval, 4.5-7.2] to 8.8 [95% confidence interval, 6.6-11.8], respectively). The prediction of small for gestational age with an estimated fetal weight of <10th percentile had a positive likelihood ratio of 6.3 to 8.5 and an area under the curve of 0.62 to 0.67. Similarly, the prediction of the neonatal composite outcome with an estimated fetal weight of <10th percentile had a positive likelihood ratio of 2.1 to 3.1 and an area under the curve of 0.55 to 0.57. When analyses were restricted to ultrasound within 4 weeks of delivery, among fetuses with an estimated fetal weight of <10th percentile, the risk of small for gestational age increased across all nomograms (odds ratio, 16.7 [95% confidence interval, 12.6-22.3] to 25.1 [95% confidence interval, 17.0-37.0]), and prediction improved (positive likelihood ratio, 8.3-15.0; area under the curve, 0.69-0.75). Similarly, the risk of neonatal composite outcome increased (odds ratio, 3.2 [95% confidence interval, 2.4-4.2] to 5.2 [95% confidence interval, 3.8-7.2]), and prediction marginally improved (positive likelihood ratio, 2.4-4.1; area under the curve, 0.60-0.62). Importantly, the risk of both being small for gestational age and having the neonatal composite outcome further increased (odds ratio, 21.4 [95% confidence interval, 13.6-33.6] to 28.7 (95% confidence interval, 18.6-44.3]), and the prediction of concurrent small for gestational age and neonatal composite outcome greatly improved (positive likelihood ratio, 6.0-10.0; area under the curve, 0.80-0.83). CONCLUSION: In this large cohort, Hadlock, recent fetal growth nomograms, and a local population-derived fetal growth reference performed comparably in the prediction of small for gestational age and neonatal composite outcomes.

Pregnant Patients with a Documented History of Penicillin Allergy and Associated Maternal and Neonatal Outcomes at a Tertiary Care Center.

OBJECTIVE: Pregnant individuals are likely to need antibiotics during the peripartum period. For pregnant individuals who report a history of penicillin allergy, non-ß-lactam antibiotics are often administered. Compared with first-line ß-lactam antibiotics, alternative antibiotics can be less effective, more toxic, and more costly. It remains unclear if being labeled with a penicillin allergy is associated with adverse maternal and neonatal outcomes. STUDY DESIGN: We conducted a retrospective cohort study of all pregnant patients who delivered a viable singleton between 24 and 42 weeks of gestation at a large academic hospital from 2013 to 2021. We compared patients who had a documented penicillin allergy history in their electronic medical record versus those who did not and examined whether there were significant differences in maternal outcomes and neonatal outcomes. Bivariable and multivariable analyses were performed. RESULTS: Of 41,943 eligible deliveries included in the analysis, 4,705 (11.2%) patients had a penicillin allergy history documented in their electronic medical record and 37,238 (88.8%) did not. Even after adjusting for potential confounders, patients with a documented penicillin allergy had a higher risk of postpartum endometritis (adjusted odds ratio [aOR]: 1.46; 95% confidence interval [CI]: 1.01-2.11) and a higher risk of their neonates having a postnatal hospital stay lasting more than 72 hours (aOR: 1.10; 95% CI: 1.02-1.18). There were no significant differences seen in the other maternal and neonatal outcomes in both bivariable and multivariable analyses. CONCLUSION: Pregnant patients who are labeled as having a penicillin allergy are more likely to have postpartum endometritis, and neonates born to mothers who are labeled as having a penicillin allergy are more likely to have a postnatal hospital stay lasting more than 72 hours. There were no other significant differences seen in pregnant patients and their newborns whether they were labeled as having a penicillin allergy history or not. However, pregnant individuals with a penicillin allergy documented in their medical record were significantly more likely to receive alternative non-ß lactam antibiotics, and may have benefitted from having more details of their allergy history available as well as proper allergy verification with testing. KEY POINTS: · It is unclear whether pregnant individuals labeled with penicillin allergies have worse obstetric outcomes.. · These individuals were significantly more likely to have endometritis and their newborns hospitalized for >72 hours.. · They were significantly more likely to receive alternative non-ß lactam antibiotics than those without documented allergies..

Low-Dose Aspirin during Pregnancy and Postpartum Bleeding.

OBJECTIVE: This study aimed to investigate whether aspirin 81 mg daily for preeclampsia prevention is associated with increased risk of postpartum blood loss at the time of delivery. STUDY DESIGN: This is a retrospective cohort study performed at a tertiary hospital from January 2018 to April 2021. Data were extracted from the electronic medical record. Patients prescribed low-dose aspirin (LDA) were compared with patients who were not. The primary outcome was a composite of postpartum blood loss, defined as: estimated blood loss (EBL) >1,000 mL, documentation of International Classification of Diseases-9/-10 codes for postpartum hemorrhage (PPH), or red blood cell (RBC) transfusion. Bivariate analysis, and unadjusted and adjusted logistic regression modeling were performed. RESULTS: Among 16,980 deliveries, 1,922 (11.3%) were prescribed LDA. Patients prescribed LDA were more likely to be >35 years old, nulliparous, obese, taking other anticoagulants, or have diagnoses of diabetes, systemic lupus erythematosus, fibroids, or hypertensive disease of pregnancy. After adjusting for potential confounders, the significant association between LDA use and the composite did not persist (adjusted odds ratio [aOR]: 1.1, 95% confidence interval [CI]: 1.0-1.3) nor did the association between EBL > 1,000 mL (aOR: 1.0, 95% CI: 0.9-1.3) and RBC transfusion (aOR: 1.3, 95% CI: 0.9-1.7). The association between LDA and PPH remained significant (aOR: 1.3, 95% CI: 1.1-1.6). Patients who discontinued LDA <7 days prior to delivery had an increased risk of the postpartum blood loss composite compared discontinuation ≥7 days (15.0 vs. 9.3%; p = 0.03). CONCLUSION: There may be an association between LDA use and increased risk of postpartum bleeding. This suggests that use of LDA outside the recommended guidelines should be cautioned and further investigation is needed to determine its ideal dosing and timing of discontinuation. KEY POINTS: · There may be an association with LDA and an increased risk of postpartum bleeding.. · Patients who discontinued LDA less than 7 days prior to delivery had an increased rate of postpartum bleeding.. · Additional research is need to determine optimal LDA dose and timing of discontinuation..

The Uptake of Telemedicine in Obstetric Care During the Early Acute Phase of the Coronavirus 2019 Pandemic.

Introduction: The early acute phase of the coronavirus disease 2019 pandemic created rapid adaptation in health care delivery. Methods: Using electronic medical record data from two different institutions located in two different states, we examined how telemedicine was integrated into obstetric care. Results: With no telemedicine use prior, both institutions rapidly incorporated telemedicine into prenatal care (PNC). There were significant patient-level and institutional-level differences in telemedicine use. Telemedicine users initiated PNC earlier and had more total visits, earlier timing of ultrasounds, and earlier diabetes screening during pregnancy compared with nonusers. There were no significant differences in delivery mode or stillbirth associated with telemedicine use at either institution. Conclusions: Rapid adoption of obstetric telemedicine maintained adequate prenatal care provision during the early pandemic, but implementation varied across institutions.

Does Antenatal Progesterone Administration Modify the Risk of Neonatal Intraventricular Hemorrhage?

OBJECTIVE: Progesterone administration has been associated with improved neurological outcomes following traumatic brain injury in adults. However, studies examining the effect of progesterone on the risk of neonatal intraventricular hemorrhage (IVH) are inconsistent. We sought to determine if maternal administration of intramuscular 17-α-hydroxyprogesterone caproate (17-OHPC) is associated with decreased rates of IVH in infants born before 32-weeks gestation. STUDY DESIGN: This is a retrospective study of liveborn singleton deliveries between 20- and 32-weeks gestation at two large academic medical centers from January 1, 2012 to August 30, 2020. Data were extracted from hospital electronic medical record data warehouses using standardized definitions and billing and diagnosis codes. We evaluated receipt of 17-OHPC in the antepartum period and diagnosis of IVH (grade I-IV, per Volpe classification) during the neonatal delivery hospitalization encounter. Bivariate and multivariate analyses were performed to examine the association between 17-OHPC and neonatal IVH adjusting for potential confounders. Odds ratio (ORs) and 95% confidence intervals (CIs) were presented. RESULTS: Among 749 neonates born between 20- and 32-week gestation, 140 (18.7%) of their mothers had received antenatal 17-OHPC and 148 (19.8%) were diagnosed with IVH after birth. No significant association was observed between maternal 17-OHPC and neonatal IVH in unadjusted (OR 1.14, 95% CI 0.72-1.78) or adjusted analyses (adjusted odds ratio 1.14, 95% CI 0.71-1.84). Independent of exposure to 17-OHPC, as expected, infants born <28-weeks gestation or those with very low birthweight (<1,500 g) were at an increased risk of IVH (OR 2.32, 95% CI 1.55-3.48 and OR 2.19, 95% CI 1.09-4.38, respectively). CONCLUSION: Antenatal maternal 17-OHPC administration was not associated with the risk of neonatal IVH. Further research may be warranted to determine whether timing, route of delivery, and duration of progesterone therapy impact rates of neonatal IVH. KEY POINTS: · This study aimed to compare the frequency of intraventricular hemorrhage in preterm neonates exposed to antenatal 17-α-hydroxyprogesterone caproate to those not exposed.. · In neonates born at <32-weeks gestation, maternal use of progesterone is not associated with the risk of intraventricular hemorrhage.. · In contrast to preclinical and adult data, this study suggests that progesterone exposure is not associated with the prevention of neonatal brain injury..

Maternal Subjective Expectations about the Technology of Skill Formation Predict Investments in Children One Year Later.

A growing literature reports significant socio-economic gaps in investments in the human capital of young children. Because the returns to these investments may be huge, parenting programs attempt to improve children's environments by increasing parental expectations about the importance of investments for their children's human capital formation. We contribute to this literature by investigating the relevance of maternal subjective expectations (MSE) about the technology of skill formation in predicting investments in the human capital of children. We develop and implement a framework to elicit and analyze MSE data. We launch a longitudinal study with 822 participants, all of whom were women in the second trimester of their first pregnancy at the date of enrollment. In the first wave of the study, during pregnancy, we elicited the woman's MSE. In the second wave, approximately one year later, we measured maternal investments using the Home Observation for the Measurement of the Environment (HOME) Inventory. The vast majority of study participants believe that the Cobb-Douglas technology of skill formation describes the process of child development accurately. We observed substantial heterogeneity in MSE about the impact of human capital at birth and investments in child development at age two. Family income explains part of this heterogeneity in MSE. The higher the family income, the higher the MSE about the impact of investment in child development. We find that a one-standard-deviation of MSE measured at pregnancy is associated with 11% of a standard deviation in investments measured when the child is approximately nine months old.

Factors associated with appropriate treatment of acute-onset severe obstetrical hypertension.

BACKGROUND: The American College of Obstetricians and Gynecologists recommends that pregnant patients receive expeditious treatment with first-line antihypertensive agents within 1 hour of confirmed severe hypertension to reduce the risk for maternal stroke. However, it is unknown how often this guideline is followed and what factors influence a patient's likelihood of receiving guideline-concordant care. OBJECTIVE: We aimed to identify factors associated with receiving guideline-concordant treatment for an obstetrical hypertensive emergency. STUDY DESIGN: We present a case-control study of all pregnant and postpartum patients who had persistent severe hypertension (≥2 systolic blood pressures ≥160 mm Hg or diastolic blood pressure ≥110 mm Hg, or both within 1 hour of each other) during their delivery hospitalization at a tertiary hospital from October 1, 2013, to August 31, 2020. Data were extracted from the hospital electronic medical records using standard definitions and billing and diagnosis codes. We defined receipt of the recommended treatment as administration of a first-line antihypertensive agent (intravenous labetalol, intravenous hydralazine, or immediate-release oral nifedipine) within 60 minutes of the first or second severe-range blood pressure measurement during their delivery hospitalization. Delayed treatment was defined as the administration of a first-line agent >60 minutes after the second elevated blood pressure measurement. Patients were considered untreated if a first-line agent was never administered. Maternal sociodemographic, clinical and pregnancy factors, and time and day of the week of the hypertensive emergency were compared among patients who received the recommended treatment, those who received delayed treatment, and those who were untreated. Bivariate analyses were performed, and multinomial and multivariable logistic regression models were used to adjust for potential confounders. RESULTS: Of the 39,918 deliveries in the cohort, 1987 (5.0%) were complicated by severe, persistent obstetrical hypertension. Of these patients, 532 (26.8%) received the recommended treatment, 356 (17.9%) received delayed treatment, and 1099 (55.3%) did not receive any first-line antihypertensive therapy. The multinomial regression models that were used to compare these 3 groups indicated that patients who received the recommended treatment were more likely to be Black (adjusted odds ratio, 1.85; 95% confidence interval, 1.36-2.51), Hispanic (adjusted odds ratio, 1.77; 95% confidence interval, 1.28-2.52), or pregnant and at <37 weeks of gestation (adjusted odds ratio, 6.65; 95% confidence interval, 5.08-8.72). Treatment was less likely if the severe obstetrical hypertension emergency occurred overnight (7:00 PM to 6:59 AM) (adjusted odds ratio, 0.79; 95% confidence interval, 0.64-0.97) or during the postpartum period (adjusted odds ratio, 0.66; 95% confidence interval, 0.51-0.86). CONCLUSION: Approximately half of obstetrical patients with at least 2 documented severely elevated blood pressure measurements did not receive the recommended antihypertensive treatment. Of those who did receive treatment, about 40% had delayed treatment. Black and Hispanic race and preterm gestation were associated with an increased likelihood of receiving the recommended treatment when compared with White race and term pregnancies. Patients whose severe obstetrical hypertension emergency occurred overnight and those who were postpartum were less likely to receive any first-line antihypertensive treatment. Overall, patients without sociodemographic and clinical risk factors for severe obstetrical hypertension or other pregnancy complications were less likely to be treated. However, treatment improved significantly over time with the implementation of targeted quality measures and specific institutional policies based on the American College of Obstetricians and Gynecologists' latest severe obstetrical hypertension management guidelines.

Perinatal outcomes in women with elevated blood pressure and stage 1 hypertension.

BACKGROUND: Hypertension was redefined in 2017 with lower diagnostic thresholds; elevated blood pressure is defined as systolic blood pressure of 120 to 129 mm Hg with diastolic blood pressure of <80 mm Hg and stage 1 hypertension as systolic blood pressure of 130 to 139 mm Hg or diastolic blood pressure of 80 to 89 mm Hg. These guidelines did not include pregnant women. There is limited information on stage 1 hypertension and pregnancy outcomes. OBJECTIVE: This study aimed to determine whether elevated blood pressure and stage 1 hypertension as newly defined by the 2017 American College of Cardiology and the American Heart Association guidelines are associated with an increased risk of hypertensive disorders of pregnancy and other adverse maternal and neonatal outcomes. STUDY DESIGN: In this retrospective cohort study, 18,801 women with singletons from 2013 to 2019 were categorized as normotensive, prehypertensive (elevated blood pressure), stage 1 hypertensive, or chronic hypertensive. Women with ≥2 systolic blood pressures of 120 to 129 mm Hg before 20 weeks' gestation were classified into the elevated blood pressure group. Women with ≥2 systolic blood pressures of 130 to 139 mm Hg or ≥2 diastolic blood pressures of 80 to 89 mm Hg before 20 weeks' gestation were assigned to the stage 1 hypertension group. Women were classified as chronic hypertensives if they had any of the following: ≥2 systolic blood pressure of ≥140 mm Hg or ≥2 diastolic blood pressure of ≥90 mm Hg before 20 weeks' gestation, a history of chronic hypertension, or antihypertensive medication use before 20 weeks' gestation. Women with pregestational diabetes, lupus, or <2 blood pressures before 20 weeks' gestation were excluded. The association of stage 1 hypertension with the risk of developing hypertensive disorders of pregnancy was estimated using multivariate logistic regression controlling for maternal sociodemographic characteristics, gestational weight gain by prepregnancy body mass index, parity, and aspirin use. Secondary outcomes included subgroups of hypertensive disorders (gestational hypertension, preeclampsia, eclampsia, and hemolysis, elevated liver enzymes, and low platelet count syndrome), gestational diabetes, placental abruption, intrauterine growth restriction, preterm birth, neonatal intensive care unit admission, stillbirth and neonatal death, and maternal intensive care unit admission. All outcomes were adjusted for potential confounders. RESULTS: Of the 18,801 women, 13,478 (71.7%) were normotensive, 2659 (14.1%) had elevated blood pressure, 1384 (7.4%) were stage 1 hypertensive, and 1280 (6.8%) were chronic hypertensive. A dose-response relationship was observed: the risk of hypertensive disorders of pregnancy increased from 4.2% in normotensive women to 6.7% (adjusted odds ratio, 1.50; 95% confidence interval, 1.26-1.79) in women with elevated blood pressure, to 10.9% (adjusted odds ratio, 2.54; 95% confidence interval, 2.09-3.08) in women with stage 1 hypertension, and 28.4% (adjusted odds ratio, 7.14; 95% confidence interval, 6.06-8.40) in women with chronic hypertension. Compared with normotensive women, women with stage 1 hypertension had an increased risk of neonatal intensive care unit admissions (15.8% vs 13.0%; adjusted odds ratio, 1.21; 95% confidence interval, 1.03-1.42), preterm birth at <37 weeks' gestation (7.2% vs 5.2%; adjusted odds ratio, 1.45; 95% confidence interval, 1.16-1.81), and gestational diabetes (14.8% vs 6.8%; adjusted odds ratio, 2.68; 95% confidence interval, 2.27-3.17). CONCLUSION: Our study demonstrates that elevated blood pressure and stage 1 hypertension, using the 2017 American College of Cardiology and the American Heart Association guideline definition, are associated with increased maternal and neonatal risk. This group of women warrants further investigation to determine whether pregnancy management can be altered to reduce maternal and neonatal morbidity.

Cytokine profiling: variation in immune modulation with preterm birth vs. uncomplicated term birth identifies pivotal signals in pathogenesis of preterm birth.

OBJECTIVES: To assess deviations in longitudinally measured cytokines with preterm birth (PTB). METHODS: Prospective longitudinal study targeting 80 subjects. Phlebotomy specimens for broad panel of cytokine analysis were obtained at three time (T) intervals: first trimester (T1: 8-14 weeks' gestation), second trimester (T2: 18-22 weeks' gestation), and third trimester (T3: 28-32 weeks' gestation). Important demographics and outcomes were tracked. Data were stratified and the target groups were analyzed as follows: "Uncomplicated" (delivered ≥37 weeks) or "Preterm Birth" (<37 weeks). Generalized Linear Modeling determined rate of change T1-T3 by outcome. RESULTS: Complete data replete with phlebotomy at all three visits were obtained on 80 women. Birth outcomes were as follows: 11 Uncomplicated Term Birth (UTB), 28 PTB, 4 low birth weight (LBW), 16 OB complications (OBC), 11 current infections (IFN), and 10 mixed complications (MC=2 or more of the above). 28 PTB were compared to 11 uncomplicated term deliveries. In both groups, T helper type 1 (TH1) cytokine (IL-1ß), pleiotrophic pro-inflammatory cytokine (IL-6), and counter-regulatory cytokine (IL-10) responses decreased over gestation, but rates of change in IL-1ß, IL-6, and IL-10 were significantly different. Stratification of women by smoking status additionally demonstrated significant variance in immune status over the course of pregnancy. CONCLUSIONS: Women delivering PTB demonstrated significant differences in cytokine trajectory over pregnancy; these data further validate key role played by immune regulation in directing pregnancy outcome. Likewise, smoking impacts longitudinal trajectory of cytokines over pregnancy.

Early Term Delivery and Breastfeeding Outcomes.

OBJECTIVE: Higher rates of adverse outcomes have been reported for early term (37 0 to 38 6 weeks) versus full term (≥ 39 0 weeks) infants, but differences in breastfeeding outcomes have not been systematically evaluated. This study examined breastfeeding initiation and exclusivity in early and full term infants in a large US based sample. METHODS: This secondary analysis included 743 geographically- and racially-diverse women from the Measurement of Maternal Stress Study cohort, and 295 women from a quality assessment at a hospital-based clinic in Evanston, IL. Only subjects delivering ≥ 37 weeks were included. Initiation of breastfeeding (IBF) and exclusive breastfeeding (EBF) were assessed via electronic medical record review after discharge. Associations of IBF and EBF with early and full term delivery were assessed via univariate and multivariate logistic regression. RESULTS: Among 872 women eligible for inclusion, 85.7% IBF and 44.0% EBF. Early term delivery was not associated with any difference in frequency of IBF (p = 0.43), but was associated with significantly lower odds of EBF (unadjusted OR 0.61, 95% CI 0.466, 0.803, p < 0.001). This association remained significant (adjusted OR 0.694, 95% CI 0.515, 0.935, p = 0.016) after adjusting for maternal diabetes, hypertensive disorders of pregnancy, cesarean delivery, maternal age, race/ethnicity, parity, Medicaid status, NICU admission, current smoking, and delivery hospital. CONCLUSIONS FOR PRACTICE: Despite comparable breastfeeding initiation frequencies, early term infants were significantly less likely to be exclusively breastfed compared to full term infants. These data suggest that women with early term infants may benefit from counseling regarding the potential for breastfeeding difficulties as well as additional breastfeeding support after delivery.

Variation in C-reactive protein at 1 month post-partum by etiology of preterm birth: selective identification of those at risk for both poor pregnancy outcome and future health complications.

Objective To assess post-partum inflammation for patients delivering prior to 34 6/7 weeks by birth etiology. Methods This was an observational study of early preterm birth (PTB) occurring between 20 0/7 and 34 6/7 weeks of gestation. Serum C-reactive protein (CRP) levels were measured 1 month post-partum. CRP measurements were compared by birth etiology. Results A total of 399 women were analyzed. Distribution of birth etiology was 35% (n = 138) preterm labor (PTL), 28% (n = 115) preterm premature rupture of membranes (pPROM), and 37% (n = 141) indicated preterm birth (IPTB). Serum CRP varied by birth etiology (P = 0.036). Women with pPROM had elevated median CRP levels compared to women with PTL (P = 0.037). IPTB demonstrated elevated CRP levels when compared to PTL (P = 0.019). Pre-eclamptic/eclamptic subjects exhibited increased median CRP levels compared to PTL (P = 0.04). Conclusion Post-partum inflammation varies by birth etiology. Such variation may serve as identification of subjects whose future pregnancies and, ultimately, overall health status may benefit from inter-pregnancy interventions aimed at reducing inflammatory-associated risk factors.

Antenatal depression, psychotropic medication use, and inflammation among pregnant women.

To evaluate the association between psychotropic medication and inflammatory biomarkers in women with antenatal depressive symptoms (ADS). In this cross-sectional secondary analysis of a prospective multicenter observational study, 723 pregnant women underwent a depression screen using the Center for Epidemiologic Studies Depression Scale (CES-D) between 12 and 21 weeks gestation. Self-reported use of medications for depression and/or anxiety was corroborated with the medical record to document exposure to pharmacotherapy. Serum was collected and inflammatory biomarkers (IFNγ, IL13, IL6, IL8, TNFα, CRP) were measured concomitantly. Women were included if they fell into one of three categories: ADS responsive to treatment (CES-D < 16 with medication), ADS not responsive to medication (CES-D ≥ 23 despite medication), and untreated ADS (CES-D ≥ 23 with no medication). Levels of inflammatory biomarkers were compared among groups and multivariable regressions performed. Of the 85 women studied, 16 (19%) had ADS responsive to treatment, 12 (14%) had ADS not responsive to medication, and 57 (67%) had untreated ADS. TNFα concentrations significantly differed (P = 0.016) across the cohorts. Post hoc bivariate analyses demonstrated that women with ADS responsive to treatment had lower serum TNFα than non-responders (p = 0.02) and women with untreated ADS (p = 0.01). There were no differences in IFNγ, IL13, IL6, IL8, or CRP among the groups. Regressions demonstrated that, compared to women with ADS responsive to treatment, non-responders or women with untreated ADS had higher TNFα levels (ß = 0.27, 95% CI 0.02-0.52 and ß = 0.23, 95% CI 0.02-0.44, respectively). Pregnant women on pharmacotherapy who respond to treatment for ADS have lower TNFα compared to women not responsive to medication or women with untreated ADS. These data suggest the possibility that either the therapeutic response in the context of pharmacotherapy is accompanied by modulation of the immune system or that pre-existing higher levels of TNFα may be associated with a poorer response to traditional pharmacotherapy.

Mothers' childhood hardship forecasts adverse pregnancy outcomes: Role of inflammatory, lifestyle, and psychosocial pathways.

Research suggests the health consequences of economic hardship can be transmitted across generations. Some of these disparities are thought to be passed to offspring during gestation. But this hypothesis has not been tested in contemporary American samples, and the mechanisms of transmission have not been characterized. Accordingly, this study had two goals: first, to determine if women exposed to economic hardship during childhood showed higher rates of adverse birth outcomes; and second, to evaluate the contribution of inflammation, psychosocial, lifestyle, and obstetric characteristics to this phenomenon. This prospective study enrolled 744 women with singleton pregnancies (59.1% White; 16.3% Black; 18.7% Latina; 5.9% Other). Childhood economic hardship was measured by self-report. Birth outcomes included length of gestation and incidence of preterm birth; birth weight percentile and small for gestational age; length of hospital stay and admission to Special Care Nursery. Analyses revealed that mothers' childhood economic hardship was independently associated with multiple adverse birth outcomes, even following adjustment for demographics, maternal education, and obstetrical confounders. Women raised in economically disadvantaged conditions had shorter gestation length and higher preterm delivery rates. Their babies had lower birth weights, were more likely to be small for gestational age, stayed in the hospital longer, and had more Special Care Nursery admissions. Mediation analyses suggested these associations arose through multiple pathways, and highlighted roles for inflammation, education, adiposity, and obstetric complications. Collectively, these findings suggest that childhood economic hardship predisposes women to adverse birth outcomes, and highlights likely behavioral and biological mechanisms.

Lessons learned from the Philadelphia Collaborative Preterm Prevention Project: the prevalence of risk factors and program participation rates among women in the intervention group.

BACKGROUND: Women who deliver preterm infants are at a much greater risk for repeating a preterm birth (PTB), compared to women without a history of PTB. However, little is known about the prevalence of the risk factors which account for this markedly increased risk. Moreover, little or nothing is known about the feasibility of providing treatments and services to these women, outside of the context of prenatal care, during the inter-conception period, which provides the best opportunity for successful risk-reduction interventions. METHODS: The Philadelphia Collaborative Preterm Prevention Project (PCPPP), a large randomized control trial designed to identify and reduce six major risk factors for a repeat preterm birth among women immediately following the delivering of a preterm infant. For the women assigned to the PCPPP treatment group, we calculated the prevalence of the six risk factors in question, the percentages of women who agreed to receive high quality risk-appropriate treatments or services, and the of rates of participation among those who were offered and eligible for these treatments or services. RESULTS: Urogenital tract infections were identified in 57% of the women, while 59% were found to have periodontal disease. More than 39% were active smokers, and 17% were assessed with clinical depression. Low literacy, and housing instability were identified in, 22 and 83% of the study sample, respectively. Among women eligible for intervention, the percentages who accepted and at least minimally participated in treatment ranged from a low of 28% for smoking, to a high of 85% for urogenital tract infection. Most PCPPP enrollees (57%) had three or more major risk factors. Participation rates associated with the PCPPP treatments or services varied markedly, and were quite low in some cases, despite considerable efforts to reduce the barriers to receiving care. CONCLUSION: The efficacy of individual level risk-reduction efforts designed to prevent preterm/repeat preterm in the pre- or inter-conception period may be limited if participation rates associated with interventions to reduce major risk factors for PTB are low. Achieving adequate participation may require identifying, better understanding, and eliminating barriers to access, beyond those associated with cost, transportation, childcare, and service location or hours of operation. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT01117922 ).

Institutional racism, neighborhood factors, stress, and preterm birth.

OBJECTIVE: Racial/ethnic disparities in the risk of preterm birth may be explained by various factors, and previous studies are limited in examining the role of institutional racism. This study focused on the following questions: what is the association between preterm birth and institutional racism as measured by residential racial segregation (geographic separation by race) and redlining (black-white disparity in mortgage loan denial); and what is the association between preterm birth and reported stress, discrimination, and neighborhood quality. DESIGN: We used data from a clinic-based sample of pregnant women (n = 3462) participating in a stress and pregnancy study conducted from 1999 to 2004 in Philadelphia, PA (USA). We linked data from the 2000 US Census and Home Mortgage Disclosure Act (HMDA) data from 1999 to 2004 and developed measures of residential redlining and segregation. RESULTS: Among the entire population, there was an increased risk for preterm birth among women who were older, unmarried, tobacco users, higher number of previous births, high levels of experiences of everyday discrimination, owned their homes, lived in nonredlined areas, and areas with high levels of segregation measured by the isolation index. Among black women, living in a redlined area (where blacks were more likely to be denied mortgage loans compared to whites) was moderately associated with a decreased risk of preterm birth (aRR = 0.8, 95% CI: 0.6, 0.99). CONCLUSION: Residential redlining as a form institutional racism and neighborhood characteristic may be important for understanding racial/ethnic disparities in pregnancy and preterm birth.

Variation in birth outcomes by mother's country of birth among non-Hispanic black women in the United States.

Rates of prematurity (PTB) and small-for-gestational age (SGA) were compared between US-born and foreign-born non-Hispanic black women. Comparisons were also made between Sub-Saharan African-born and Caribbean-born black women and by maternal country of birth within the two regions. Comparisons were adjusted for sociodemographic, health behavioral and medical risk factors available on the birth record. Birth record data (2008) from all states (n = 27) where mother's country of birth was recorded were used. These data comprised 58 % of all singleton births to non-Hispanic black women in that year. Pearson Chi square and logistic regression were used to investigate variation in the rates of PTB and SGA by maternal nativity. Foreign-born non-Hispanic black women had significantly lower rates of PTB (OR 0.727; CI 0. 726, 0.727) and SGA (OR 0.742; CI 0.739-0.745) compared to US-born non-Hispanic black women in a fully adjusted model. Sub-Saharan African-born black women compared to Caribbean-born black women had significantly lower rates of PTB and SGA. Within each region, the rates of PTB and SGA varied by mother's country of birth. These differences could not be explained by adjustment for known risk factors obtained from vital records. Considerable heterogeneity in rates of PTB and SGA among non-Hispanic black women in the US by maternal nativity was documented and remained unexplained after adjustment for known risk factors.

Association Between Intrapartum Nitrous Oxide for Labor Analgesia and Short-Term Neonatal Outcomes.

OBJECTIVE: To evaluate the association between intrapartum nitrous oxide use and adverse short-term neonatal outcomes. METHODS: This was a retrospective cohort study of individuals with singleton gestations at 35 or more weeks who attempted labor and delivered at an academic hospital between June 1, 2015, and February 28, 2020. Data were extracted from the electronic medical record using billing and diagnostic codes. Patients were classified based on whether they received no intrapartum analgesia or received nitrous oxide only. Those who received other analgesia types were excluded. The primary outcome was neonatal intensive care unit (NICU) admission. Secondary outcomes included Apgar score less than 7 at 1 minute and 5 minutes, respiratory composite outcome (including meconium aspiration syndrome, neonatal bronchopulmonary disorders, neonatal transient tachypnea, and other neonatal respiratory distress that required NICU admission), hypoglycemia, and hyperbilirubinemia. Univariable and multivariable analyses were used to estimate the association between nitrous oxide exposure intrapartum and the selected outcomes. RESULTS: Of 6,047 included, 4,153 (68.7%) received no analgesia, and 1,894 (31.3%) received nitrous oxide only. In comparison with individuals who received no analgesia, those who received nitrous oxide were more likely to be nulliparous, be of Black racial identity, have noncommercial insurance, and be less likely to deliver by intrapartum cesarean. The reception of nitrous oxide, compared with the reception of no analgesia, was associated with a lower likelihood of NICU admission (6.4% vs 8.1%; adjusted odds ratio [aOR] 0.77, 95% CI, 0.62-0.96) and an increased likelihood of neonatal hyperbilirubinemia (aOR 1.23, 95% CI, 1.08-1.41). Inhaled nitrous oxide exposure, in comparison with the reception of no analgesia, was not associated with the other secondary outcomes, including Apgar score less than 7 at 1 minute (odds ratio [OR] 0.74, 95% CI, 0.50-1.10) or 5 minutes (OR 0.91, 95% CI, 0.32-2.60), respiratory composite outcome (OR 0.91, 95% CI, 0.70-1.17), and hypoglycemia (OR 0.82, 95% CI, 0.64-1.05). CONCLUSION: In this single-center retrospective cohort of low-risk patients, intrapartum inhaled nitrous oxide, compared with the reception of no analgesia, was associated with a decreased risk for NICU admission but with an increased risk for hyperbilirubinemia; other outcomes did not differ. These findings may be used to counsel patients when considering nitrous oxide for labor analgesia.

Co-existing chronic hypertension and hypertensive disorders of pregnancy and associated adverse pregnancy outcomes.

OBJECTIVE: Chronic hypertension (CHTN) causes vascular damage and resistance in the pregnant person and malperfusion in the placenta which may worsen the endothelial dysfunction of hypertensive disorders of pregnancy (HDP). These conditions frequently co-exist. A cumulative effect has been inconsistently demonstrated in prior studies, and it is unclear how co-existing hypertensive conditions affect pregnancy outcomes. We sought to examine maternal and neonatal outcomes in pregnancies affected by co-existing CHTN and HDP and compare these outcomes to those of pregnancies which were unaffected or affected by either condition alone. METHODS: This is a retrospective cohort study of singleton deliveries at a single institution 1 October 2013 to 1 October 2021. Data were extracted from the electronic medical record using standardized definitions and billing and diagnosis codes. Pregnant people with no evidence of hypertensive condition were compared to those with CHTN only, HDP only, and co-existing CHTN and HDP. Demographics, baseline clinical data, and use of aspirin or antihypertensive medications were assessed. Maternal outcomes included cesarean delivery, critical range blood pressure, intensive care unit (ICU) admission, and death. Neonatal outcomes included preterm birth <37 weeks' gestation, small for gestational age (SGA) birthweight, ICU admission, and a morbidity composite. Bivariate tests of association were performed using Chi-square test. Crude and adjusted odds ratios (aORs) were calculated using logistic regression for three maternal and four neonatal outcomes. Descriptive statistics and multivariable analyses were performed. RESULTS: Of 40,840 eligible people, 1451 (3.6%) had CHTN only; 5213 (12.8%) had HDP only; and 1890 (4.6%) had co-existing CHTN and HDP. Though odds of adverse maternal and neonatal outcomes were significantly increased for all hypertensive groups relative to the unaffected referent group, co-existing CHTN and HDP had the highest odds of cesarean delivery (aOR 1.60; 95% confidence interval (CI) 1.45-1.77), critical blood pressure (OR 41.54; 95% CI 35.96-47.99), maternal ICU admission or death (aOR 3.52; 95% CI 2.65-4.67), preterm birth (aOR 2.76; 95% CI 2.41-3.16), and SGA birthweight (aOR 1.61; 95% CI 1.39-1.87). CONCLUSIONS: Hypertensive disorders of pregnancy in the setting of CHTN are associated with the highest odds of serious consequences on the pregnant person and neonate independent of maternal comorbidities and prematurity. Antihypertensive medication use lowers the odds of some adverse outcomes. Patients should be informed of heightened risks, but optimal management remains unclear.

New models for large prospective studies: is there a risk of throwing out the baby with the bathwater?

Manolio et al. (Am J Epidemiol. 2012;175:859-866) proposed that large cohort studies adopt novel models using "temporary assessment centers" to enroll up to a million participants to answer research questions about rare diseases and "harmonize" clinical endpoints collected from administrative records. Extreme selection bias, we are told, will not harm internal validity, and "process expertise to maximize efficiency of high-throughput operations is as important as scientific rigor" (p. 861). In this article, we describe serious deficiencies in this model as applied to the United States. Key points include: 1) the need for more, not less, specification of disease endpoints; 2) the limited utility of data collected from existing administrative and clinical databases; and 3) the value of university-based centers in providing scientific expertise and achieving high recruitment and retention rates through community and healthcare provider engagement. Careful definition of sampling frames and high response rates are crucial to avoid bias and ensure inclusion of important subpopulations, especially the medically underserved. Prospective hypotheses are essential to refine study design, determine sample size, develop pertinent data collection protocols, and achieve alliances with participants and communities. It is premature to reject the strengths of large national cohort studies in favor of a new model for which evidence of efficiency is insufficient.