Janice E. Whitty

Antimicrobial peptides in amniotic fluid: defensins, calprotectin and bacterial/permeability-increasing protein in patients with microbial invasion of the amniotic cavity, intra-amniotic inflammation, preterm labor and premature rupture of membranes

Objective: Neutrophil defensins (HNP 1-3), bactericidal/permeability-increasing protein (BPI) and calprotectin (MRP8/14) are antimicrobial peptides stored in leukocytes that act as effector molecules of the innate immune response. The purpose of this study was to determine whether parturition, premature rupture of the membranes (PROM) and microbial invasion of the amniotic cavity (MIAC) are associated with changes in amniotic fluid concentrations of these antimicrobial peptides. Study design: Amniotic fluid was retrieved by amniocentesis from 333 patients in the following groups: group 1, mid-trimester with a subsequent normal pregnancy outcome (n = 84); group 2, preterm labor and intact membranes without MIAC who delivered at term (n = 36), or prematurely (n = 52) and preterm labor with MIAC (n = 26); group 3, preterm PROM with (n = 26) and without (n = 26) MIAC; and group 4, term with intact membranes in the absence of MIAC, in labor (n = 52) and not in labor (n = 31). The concentrations of HNP 1-3, BPI and calprotectin in amniotic fluid were determined by specific and sensitive immunoassays. Placentae of patients in both preterm labor with intact membranes and preterm PROM groups who delivered within 72 h of amniocentesis were examined. Non-parametric statistics, receiver-operating characteristic (ROC) curves and Cox regression models were used for analysis. A p value of < 0.05 was considered statistically significant. Results: Intra-amniotic infection was associated with a significant increase in amniotic fluid concentrations of immunoreactive HNP 1-3, BPI and calprotectin in both women with preterm labor and intact membranes, and women with preterm PROM. Preterm PROM was associated with a significant increase in amniotic fluid concentrations of immunoreactive HNP 1-3, BPI and calprotectin. Preterm parturition was associated with a significant increase in amniotic fluid concentrations of immunoreactive HNP 1-3, BPI and calprotectin, while parturition at term was associated with a significant increase in amniotic fluid concentrations of immunoreactive HNP 1-3. Among patients with preterm labor and intact membranes, elevation of amniotic fluid HNP 1-3, BPI and calprotectin concentrations was associated with intra-amniotic inflammation, histological chorioamnionitis and a shorter interval to delivery. Conclusion: MIAC, preterm parturition and preterm PROM are associated with increased amniotic fluid concentrations of immunoreactive HNP 1-3, BPI and calprotectin. Moreover, elevated amniotic fluid concentrations of BPI, immunoreactive HNP 1-3 and calprotectin are associated with intra-amniotic inflammation, histological chorioamnionitis and shorter amniocentesis-to-delivery interval in patients presenting with preterm labor with intact membranes.

Clinical Significance of Increasing Histologic Severity of Acute Inflammation in the Fetal Membranes and Umbilical Cord

The purpose of this study was to determine the importance of varying histologic stages of inflammation in the placental membranes and cord. Acute inflammation was histologically staged in fetal membranes and umbilical cord sections from 2899 placentas received from consecutive singleton deliveries. Then clinical data were collected for a subset of randomly selected placentas with stage 1 through stage 4 membrane inflammation (n = 212) and without significant inflammation (stage 0, n = 216). Statistical analyses revealed that increasing stage of membrane inflammation was associated with an increasing rate of funisitis, perinatal death, and preterm birth (P < .05). Inflammation permeating the entire trophoblastic layer of the chorion (stage 1) was associated with clinical symptoms of intrauterine infection and thus was an important pathologic finding. Acute necrotizing chorioamnionitis was very strongly associated with perinatal death and preterm birth. Acute funisitis was a more specific but less sensitive marker for perinatal complications than inflammation in the membranes. With increasing stage of funisitis, there was an increased incidence of clinical symptoms of intrauterine infection, preterm birth, and perinatal death. Almost three-fourths of the cases with histologic evidence of membrane inflammation were clinically silent. In conclusion, increasing histologic stages of inflammation of the membranes and cord are associated with an increased rate of perinatal morbidity and mortality. Stage I membrane inflammation provides a clinically acceptable minimum threshold for the reporting of pathologic changes.

Does delivery improve maternal condition in the respiratory-compromised gravida?

Objective To describe the effect of delivery on respiratory status and outcome in the respiratory-compromised pregnant woman. Methods During 1990-1994, 10 patients requiring intubation for respiratory compromise who delivered during ventilatory support were identified by International Classification of Diseases, Ninth Revision codes. Charts were reviewed retrospectively for cardiorespiratory variables and outcome. Results Pneumonia led to intubation in all but one case. The onset of labor was spontaneous in eight. Three were delivered by cesarean. Mechanical ventilation was used for a median (range) of 7 (2-22) days in surviving patients. Fraction of inspired oxygen requirements decreased an average of 28% by 24 hours after delivery. Positive end-expiratory pressure requirements remained unaltered. Surviving patients remained intubated for a median (range) of 2.6 (1–19) days postpartum. Three women died, all after vaginal delivery (days 4–14). Conclusion Delivery of respiratory-compromised gravidas resulted in a 28% reduction in fraction of inspired oxygen requirement within 24 hours after delivery. Although most patients were then able to be maintained below critical fraction of inspired oxygen requirement levels (under 0.6), dramatic improvement in overall respiratory function was not observed uniformly. Given the limited benefit of delivery on maternal oxygenation, along with the inherent risks of labor induction in this critically ill population, caution should be exercised in initiating the induction process electively.

Maternal cardiac arrest in pregnancy.

Cardiac arrest in pregnancy is rare, but almost 10% of maternal deaths result from cardiac arrest. Despite our best efforts, we know that more than half of resuscitation attempts in the nonpregnant population do not succeed. Tragically, even when cardiac activity is restored, only about half of ventricular fibrillation cardiac arrest victims admitted to the emergency department survive and go home. This means that three out of four cardiopulmonary resuscitation (CPR) attempts will be unsuccessful. Attempts at CPR during pregnancy may be impeded by the physiologic changes that take place during pregnancy, including the gravid uterus. Therefore, the obstetrician/gynecologist must understand the physiologic changes that occur in pregnancy and affect the potential for resuscitation. CPR is a team effort. Although the obstetrician/gynecologist may not actually “run the code” in the majority of circumstances, basic life support (BLS) and advanced cardiac life support (ACLS) certifications provide the framework to participate as an integral member of the resuscitation team. This chapter is not meant to be a comprehensive work on CPR. However, after review, one should be familiar with the causes of cardiopulmonary arrest in pregnancy, understand the impact of pregnancy on resuscitation efforts, and have a basic understanding of the efforts needed to resuscitate the gravid patient. In addition, we will discuss perimortem cesarean and its impact on maternal and fetal outcome. Unfortunately, most of the literature documenting management and outcome of cardiac arrest in pregnancy consists of case reports, expert advice, and anecdotal information. Therefore, the content of this chapter will be based on that literature and the thoughtful application of the principles of resuscitation to accommodate the needs of the pregnant woman and her fetus.

Circulating angiogenic and antiangiogenic factors in women with eclampsia

OBJECTIVE The objective of the study was to determine whether eclampsia has a different circulating profile of angiogenic (placental growth factor [PlGF]) and antiangiogenic factors (soluble vascular endothelial growth factor receptor-1 [sVEGFR-1] and soluble endoglin [sEng]) from severe preeclampsia. STUDY DESIGN This cross-sectional study included pregnant women in the following groups: (1) normal pregnancy (n = 40); (2) severe preeclampsia (n = 40); and (3) eclampsia (n = 20). Maternal serum PlGF, sVEGFR-1, and sEng concentrations were determined using an enzyme-linked immunosorbent assay. RESULTS The study results included the following: (1) the median concentration of sVEGFR-1 and sEng was higher and of PlGF was lower in severe preeclampsia or eclampsia than in normal pregnancy (P < .001 for all); and (2) the median concentrations of these 3 analytes did not differ significantly between patients with severe preeclampsia and those with eclampsia. CONCLUSION Eclampsia is associated with higher maternal circulating concentrations of sVEGFR-1 and sEng and lower concentrations of PlGF than normal pregnancy but with similar concentrations to severe preeclampsia. These findings suggest that eclampsia shares a common pathogenic pathway as severe preeclampsia.

Serum ionized magnesium levels in normal and preeclamptic gestation

Objective To compare serum levels of ionized and total magnesium with those of ionized calcium, total calcium, sodium, and potassium over the course of pregnancy in normal women and in women who develop preeclampsia. Methods We collected venous serum samples from 31 pregnant women during their first, second, and third trimesters. Gestational ages ranged from 6 to 37 weeks. Samples were analyzed for ionized and total magnesium, ionized and total calcium, sodium, and potassium using a biomedical chemistry analyzer. Data were analyzed with repeated-measures analysis of variance and two-way repeated-measures analysis of variance. Results In 22 normal pregnant women, both serum ionized and total magnesium levels decreased significantly with increasing gestational age. No changes in sodium, potassium, or ionized or total calcium were observed. Nine of the 31 subjects developed preeclampsia by term; serum total magnesium levels decreased significantly by the second trimester in these women compared with those of normal pregnant women. Conclusion Our results provide evidence of decreases in ionized and total magnesium levels with increasing gestational age during normal pregnancy, as well as evidence of a magnesium disturbance in women who later develop preeclampsia. Future studies of magnesium balance in women at risk for developing complications of pregnancy are indicated.

Eclampsia: A neurological perspective

Eclampsia is a poorly understood disorder characterized by seizures or unexplained coma in setting of gestational hypertension. Its neurological manifestations are varied and are an important cause of the morbidity and mortality associated. We present a comprehensive prospective study of forty women recruited over four years describing neurological symptoms and signs, neuroimaging and laboratory studies as well as prognosis including 3-6 months follow-up. The seizures occurred in the postpartum period in majority of women (55%), while 45% had seizures before labor, and the rest (5%) during labor. Interestingly, one third of the women suffered their first seizures more than 48 h postpartum (late postpartum eclampsia). A sizable minority suffered more than one seizure and some had documented partial seizures. Headache preceded seizures by more than a day and was described as throbbing or pounding pain by most. The visual symptoms in decreasing frequency were blurring, blindness, scotoma and visual processing deficits. The most common finding during the neurological exam was memory deficits, followed by increased deep tendon reflexes (asymmetric in some), visual perception deficits, visual information processing deficits, altered mental status and cranial nerve deficits. Intracranial or intraspinal pressure when examined was elevated. Among neuroimaging studies, MRI was more sensitive compared to CT scan. The MRI abnormalities included both white as well as gray matter and the most common location of abnormalities was high frontal/parietal lobe. The laboratory studies revealed proteinuria in majority, but not in all. The liver function tests were abnormal in many, while few patients had HELLP syndrome. The neurological deficits resolved by the time of discharge in all. At follow-up, some patients developed new neurological problems such as recurrent headaches or seizures.

Effects of gestational alcohol exposure on the fatty acid composition of umbilical cord serum in humans

This study examined the effects of maternal periconceptional alcohol intake on polyunsaturated fatty acid (PUFA) concentrations in human neonates. The area percentage of each fatty acid in cord blood serum from 12 infants born to control women (who consumed <2 mL absolute ethanol/d) was compared with that of 9 infants born to women whose periconceptional alcohol intake averaged > or = 30mL absolute ethanol/d. Periconceptional alcohol use was associated with a 30% increase in the proportion of docosahexaenoic acid (22:6n-3) in cord blood (3.0% of total lipid in control infants compared with 3.9% in alcohol-exposed infants; P < 0.01). The rise in the proportion of 22:6n-3 was responsible for increases in the ratio of n-3 to n-6 fatty acids and the ratio of long-chain n-3 to n-6 fatty acids (P < 0.055). Examination of the lipid-class fatty acid profile indicated that serum lipid alterations were localized to the cholesterol esters; 22:6n-3 in the cholesterol esters of alcohol-exposed infants increased 54% (P < 0.011) and arachidonic acid increased 55% (P < 0. 005). The relative fatty acyl composition of maternal serum showed a significant increase in 18:0 fatty acids in the alcohol-exposed group (25%, P < 0.005) but there were no changes in the other fatty acids. The increase in the proportion of 22:6n-3 was unexpected but is consistent with the hypothesis that this essential lipid may be conserved selectively. These results imply that the lifelong neurobehavioral and sensory dysfunction in fetal alcohol syndrome and other alcohol-related neurodevelopmental disorders may be due in part to PUFA dysregulation.

Alcohol Consumption in Pregnant, Black Women Is Associated With Decreased Plasma and Erythrocyte Docosahexaenoic Acid

BACKGROUND Inner-city, black women are among those groups that are at higher risk for having infants with fetal alcohol spectrum disorders that can include life-long neurobehavioral and cognitive impairments. Chronic alcohol consumption can decrease amounts of docosahexaenoic acid (DHA), a fatty acid that is essential for optimal infant neural and retinal development in a variety of tissues. METHODS Black women who presented at an inner-city antenatal clinic for their first prenatal visit were recruited into a longitudinal, observational study. Alcohol intake was determined by a structured interview. Participants provided blood specimens and completed food frequency surveys at 24 weeks of gestation, infant delivery, and 3 months postpartum. Fatty acid composition analyses were completed on 307, 260, and 243 for plasma and 278, 261, and 242 erythrocyte specimens at 24 weeks of gestation, delivery, and 3 months postpartum, respectively. RESULTS Proportion of drinking days at the first prenatal visit was associated with decreased DHA in plasma and erythrocytes throughout the study. This association was the strongest at 24 weeks of gestation. In addition, an interaction between proportion of drinking days at the time of conception and ounces of absolute alcohol per drinking day at the time of conception was detected and demonstrated that, in daily drinkers, high intakes of alcohol are associated with decreased DHA and arachidonic acid (AA) concentrations in plasma. CONCLUSIONS Frequent and high intakes of alcohol that have been previously associated with fetal alcohol spectrum disorders are also associated with decreased maternal DHA and AA plasma concentrations. The present findings indicate that maternal DHA deficiency is associated with high-risk drinking and may contribute to the mechanism(s) of alcohol-related neurodevelopmental disorders.

Brain MRI in peripartum seizures: usefulness of combined T2 and diffusion weighted MR imaging

Peripartum seizure is a serious disease with significant morbidity and mortality for women and their unborn children. The underlying etiologies are varied, with eclampsia and venous stroke being the most common causes. T2 weighted MR images of the brain show hyperintense lesions in either condition. Diffusion weighted MR images (DWI) of the brain is abnormal in strokes. We report three cases of eclampsia with abnormal T2 weighted images, but normal DWI. Diffusion weighted MR images in association with T2 weighted MR images can be extremely helpful in evaluation of women with new onset peripartum seizures.