Donna Johnson

Host factors in amniotic fluid and breast milk that contribute to gut maturation.

The gut represents a complex organ system with regional differences, which reflect selective digestive and absorptive functions that change constantly in response to bodily requirements and the outside milieu. As a barrier to the external environment, gut epithelium must be renewed rapidly and repeatedly. Growth and renewal of gut epithelial cells is dependent on controlled cell stimulation and proliferation by a number of signaling processes and agents, including gut peptides—both endogenous and exogenous sources. This cascade of events begins during fetal development; with the ingestion of amniotic fluid, this process is enhanced and continued during infancy and early childhood through the ingestion of human milk. Events influenced by amniotic fluid during fetal development and those influenced by human milk that unfold after birth and early childhood to render the gut mature are presented.

Vitamin D and Its Role During Pregnancy in Attaining Optimal Health of Mother and Fetus

Despite its discovery a hundred years ago, vitamin D has emerged as one of the most controversial nutrients and prohormones of the 21st century. Its role in calcium metabolism and bone health is undisputed but its role in immune function and long-term health is debated. There are clear indicators from in vitro and animal in vivo studies that point to vitamin D’s indisputable role in both innate and adaptive immunity; however, the translation of these findings to clinical practice, including the care of the pregnant woman, has not occurred. Until recently, there has been a paucity of data from randomized controlled trials to establish clear cut beneficial effects of vitamin D supplementation during pregnancy. An overview of vitamin metabolism, states of deficiency, and the results of recent clinical trials conducted in the U.S. are presented with an emphasis on what is known and what questions remain to be answered.

Maternal super-obesity (body mass index ≥ 50) and adverse pregnancy outcomes

Objective. To determine if pregnancy complications are increased in super‐obese (a body mass index (BMI) of 50 or more) compared to other, less obese parturients. Design. Cross‐sectional study. Setting and population. All 19,700 eligible women, including 425 (2.2%) super‐obese women with singleton births between 1996 and 2007 delivering at a tertiary referral center, identified using a perinatal research database. Methods. Bivariate and trend analyses were used to assess the relation between super‐obesity and various pregnancy complications compared to other well‐established BMI categories. Adjusted odds ratios (ORs) were calculated using multivariable logistic regression techniques. Main outcome measures. Outcomes for adjusted and unadjusted analyses were small‐for‐gestational age (SGA) birth, large‐for‐gestational age (LGA) birth, preeclampsia, gestational diabetes mellitus (GDM), fetal death, preterm birth, placental abruption, cesarean delivery, and Apgar scores < 7. Results. Compared to all other obese and non‐obese women, super‐obese women had the highest rates of preeclampsia, GDM, LGA, and cesarean delivery (all p < 0.05 for trend test). Super‐obesity was also associated with a 44% reduction in SGA compared to all other women (OR 0.55, 95% confidence interval (CI) 0.40–0.76) and a 25% reduction compared to other, less obese women (OR 0.75, 95% CI 0.54–1.03). Super‐obesity was positively associated with LGA, GDM, preeclampsia, cesarean delivery, and a 5‐minute Apgar score < 7 compared to all other women after controlling for important confounders. Conclusion. Super‐obesity is associated with higher rates of pregnancy complications compared to women of all other BMI classes, including other obese women.

Maternal vitamin D and fetal growth in early-onset severe preeclampsia.

OBJECTIVE Recently, vitamin D deficiency has been associated with increased risks for preeclampsia and diagnosis of early-onset, severe preeclampsia (EOSPE). The purpose of this investigation was to examine the association between vitamin D levels and small-for-gestational age (SGA) in patients with EOSPE. STUDY DESIGN Patients with EOSPE were recruited, and demographics, outcomes, and plasma were collected. We assessed 25-hydroxyvitamin D (25[OH]D) by radioimmunoassay and reported our findings in nanograms per milliliter. Results were analyzed by Mann-Whitney U test and Spearman correlation and were reported as median (Q1-Q3). RESULTS In patients with EOSPE (n = 56), 25(OH)D was lower in patients with SGA (16.8 ng/mL; range, 8.9-23 ng/mL) vs normal fetal growth (25.3 ng/mL; range, 16-33 ng/mL; P = .02). 25(OH)D was correlated significantly with percentile growth at delivery (ρ = 0.31; P = .02). CONCLUSION Vitamin D is lower among patients with SGA in EOSPE than those without growth retardation. We suspect that vitamin D may impact fetal growth through placental mechanisms.

Early-onset severe preeclampsia: induction of labor vs elective cesarean delivery and neonatal outcomes

OBJECTIVE The purpose of this study was to describe the success rate of and analyze differences in neonatal outcomes with labor induction, compared with elective cesarean delivery in women with early-onset severe preeclampsia. STUDY DESIGN We conducted a cross-sectional study of women with severe preeclampsia who required delivery between 24 and 34 weeks of gestation. Bivariate and multivariable regression analyses were used to determine factors that were associated with assignment to, success of, and odds of neonatal outcomes after induction of labor. RESULTS Fifty-seven and four-tenths percent of 491 women underwent induction of labor. Vaginal delivery occurred in 6.7%, 47.5%, and 68.8% of women who underwent labor induction between 24 and 28, 28 and 32, and 32 and 34 weeks of gestation, respectively. Induction of labor was not associated with an increase in neonatal morbidity or mortality rate after we controlled for gestational age and other confounders. CONCLUSION Neonatal outcomes are not worsened by induction of labor in women with early-onset severe preeclampsia, although it is rarely successful at <28 weeks of gestation.

Association of maternal vitamin D and placenta growth factor with the diagnosis of early onset severe preeclampsia

OBJECTIVE Decreased maternal 25-hydroxyvitamin D (25-OH-D) and placenta growth factor (PlGF) have both been associated with the diagnosis of early onset severe preeclampsia (EOSPE). This investigation aimed to define the association of these biomarkers with EOSPE. STUDY DESIGN Patients with EOSPE (n = 40) and healthy controls (n = 40) were recruited and information on demographics, outcomes, and plasma was collected at diagnosis of EOSPE or gestational age-matched controls. 25-OH-D was assessed by radioimmunoassay and reported in nanogram per milliliter. PlGF was assessed by enzyme-linked immunosorbent assay and reported in picogram per milliliter. Kruskal-Wallis test was used to compare biomarkers between groups. Multivariable logistic regression was used to determine associations between 25-OH-D or PlGF and the diagnosis of EOSPE. RESULTS In EOSPE, both 25-OH-D and PlGF were decreased significantly compared with controls. After controlling for age, race, body mass index, and gestational age at sample collection, both 25-OH-D (adjusted odds ratio 0.14 [0.05, 0.36]) and PlGF (adjusted odds ratio 0.03 [0.01, 0.24] were significantly associated with diagnosis of ESOPE (p < 0.001 for both markers). CONCLUSION PlGF and 25-OH-D are both associated with the diagnosis of EOSPE. These biomarkers may be helpful in development of novel rapid diagnostic tests for preeclampsia.

Digoxin immune fab treatment for severe preeclampsia.

We evaluated the efficacy, safety, and biological mechanisms of digoxin immune Fab (DIF) treatment of severe preeclampsia. Fifty-one severe preeclamptic patients were randomized in double-blind fashion to DIF ( N = 24) or placebo ( N = 27) for 48 hours. Primary outcomes were change in creatinine clearance (CrCl) at 24 to 48 hours and antihypertensive drug use. Serum sodium pump inhibition, a sequela of endogenous digitalis-like factors (EDLF), was also assessed. CrCl in DIF subjects was essentially unchanged from baseline versus a decrease with placebo (-3 +/- 10 and -34 +/- 10 mL/min, respectively, P = 0.02). Antihypertensive use was similar between treatments (46 and 52%, respectively, P = 0.7). Serum sodium pump inhibition was decreased with DIF compared with placebo at 24 hours after treatment initiation (least squares mean difference, 19 percentage points, P = 0.03). DIF appeared to be well tolerated. These results suggest DIF prevents a decline in renal function in severe preeclampsia by neutralizing EDLF. Sodium pump inhibition was significantly improved. Further research is warranted.

Prediction of pelvic organ prolapse using an artificial neural network

OBJECTIVE The objective of this investigation was to test the ability of a feedforward artificial neural network (ANN) to differentiate patients who have pelvic organ prolapse (POP) from those who retain good pelvic organ support. STUDY DESIGN Following institutional review board approval, patients with POP (n = 87) and controls with good pelvic organ support (n = 368) were identified from the urogynecology research database. Historical and clinical information was extracted from the database. Data analysis included the training of a feedforward ANN, variable selection, and external validation of the model with an independent data set. RESULTS Twenty variables were used. The median-performing ANN model used a median of 3 (quartile 1:3 to quartile 3:5) variables and achieved an area under the receiver operator curve of 0.90 (external, independent validation set). Ninety percent sensitivity and 83% specificity were obtained in the external validation by ANN classification. CONCLUSION Feedforward ANN modeling is applicable to the identification and prediction of POP.

Examining the effect of maternal obesity on outcome of labor induction in patients with preeclampsia.

Objective The objective of this investigation was to evaluate the effect of maternal obesity, as measured by prepregnancy body mass index (BMI), on the mode of delivery in women undergoing indicated induction of labor for preeclampsia. Study Design Following Institutional Review Board (IRB) approval, patients with preeclampsia who underwent an induction of labor from 1997 to 2007 were identified from a perinatal information database, which included historical and clinical information. Data analysis included bivariable and multivariable analyses of predictor variables by mode of delivery. An artificial neural network was trained and externally validated to independently examine predictors of mode of delivery among women with preeclampsia. Results Six hundred and eight women met eligibility criteria and were included in this investigation. Based on multivariable logistic regression (MLR) modeling, a 5-unit increase in BMI yields a 16% increase in the odds of cesarean delivery. An artificial neural network trained and externally validated confirmed the importance of obesity in the prediction of mode of delivery among women undergoing labor induction for preeclampsia. Conclusion Among patients who are affected by preeclampsia, obesity complicates labor induction. The risk of cesarean delivery is enhanced by obesity, even with small increases in BMI. Prediction of mode of delivery by an artificial neural network performs similar to MLR among patients undergoing labor induction for preeclampsia.

A new method to examine very low birth weight fetal and hebdomadal mortality in a regionalized system of perinatal care.

Objective: Aggressive maternal transport of very low birth weight (VLBW) live births from community hospitals to regional perinatal centers may artificially increase community fetal death rates. By allocating maternal transports according to the location of antepartum and intrapartum care and separately computing antepartum and intrapartum fetal mortality rates, a more appropriate measure of hospital-based mortality may be determined. Method: Delivery charts were reviewed for 568 VLBW deliveries (including 97 fetal deaths and 77 hebdomadal deaths) occurring between 1990 and 1992 in a geographically defined perinatal region. Maternal transports were analyzed with community hospitals for antepartum mortality rates and with the regional center for intrapartum mortality rates. Results: Using traditional methods, the fetal mortality rates for community hospitals and the regional center were antepartum 385.1 vs. 45.2, respectively, and intrapartum 120.9 vs. 24.9, respectively. When regional center live births (maternal transports) are placed with community hospitals for analysis of antepartum mortality, the new antepartum mortality rates were 185.7 vs. 72.8, respectively. The hebdomadal mortality rate for community hospitals was 250.0 as compared to 145.8 for the regional center. Conclusion: Maternal transports to a regional center represent successful antepartum management by community care providers. Even though they delivered in the regional center, they should be analyzed with community hospitals for antepartum fetal mortality comparisons. Therefore, antepartum and intrapartum fetal mortality should be examined separately in a functioning regionalized perinatal care program where the location of patient care differs from location of delivery.