M. Camille Hoffman

Measures of Maternal Stress and Mood in Relation to Preterm Birth.

OBJECTIVE: To investigate the relationships between psychological and physiologic measures of stress, mood, and gestational age at delivery and preterm birth. METHODS: This prospective cohort study recruited healthy women in the early second trimester who were 18–45 years of age. Validated psychological measures of perceived stress, depressive symptoms, and anxiety were completed at 16, 22, 28, 34, and 40 weeks of gestation. Cortisol concentration was measured in maternal hair at 16, 28, and 40 weeks of gestation to approximate first-, second-, and third-trimester levels of physiologic stress. Statistical methods included: analyses of variance, t tests, &khgr;2, Pearson correlations, regression modeling, and mediation analysis as appropriate. Hair cortisol concentrations were natural log-transformed to normalize values. RESULTS: Eleven (12%) of the 90 included women had a spontaneous preterm birth or preterm premature rupture of membranes. Perceived stress at 16 weeks of gestation correlated with both second-trimester cortisol concentration (r=0.28, P=.007) and earlier gestational age at delivery (r=−0.30, P<.01). Gestational age at delivery was also negatively correlated with cortisol concentration in the second trimester (r=−0.25, P=.02) and second-trimester cortisol concentration was higher in preterm- (2.7±0.4 log-transformed pg/mg) compared with term- (2.0±0.7 log-transformed pg/mg, P<.001) delivered women. Using mediation statistics, the association between the psychological measure, the physiologic measure, and gestational age at delivery was mainly driven by increased physiologic stress (hair cortisol concentration) in the second trimester (difference in coefficients [standard error]=−0.05 [0.02]). CONCLUSION: Higher perceived stress in the second trimester is associated with both elevated second-trimester hair cortisol concentration and gestational age at delivery. Physiologic measure of stress in the second trimester appears most strongly associated with preterm birth. Identification and amelioration of early pregnancy stressors may attenuate physiologic stress and ultimately affect preterm birth.

Maternal and Fetal Alternative Complement Pathway Activation in Early Severe Preeclampsia

We sought to determine whether alternative complement activation fragment Bb (Bb) levels are elevated in the maternal, fetal, and placental blood in cases of severe preeclampsia (PE) compared with normotensive controls.

Gestational age at initiation of 17-hydroxyprogesterone caproate (17P) and recurrent preterm delivery

Objective. To compare rates of recurrent preterm birth between women starting treatment with 17α-hydroxyprogesterone caproate (17P) at 16–20.9 weeks of gestation versus 21–26.9 weeks. Methods. Women enrolled in an outpatient program of education, nursing assessment and weekly 17P injections beginning at 16–26.9 weeks were eligible. Included were patients with singleton pregnancies and a history of preterm delivery (PTD). Pregnancy outcome was compared between women starting 17P at 16–20.9 weeks (n = 156) and those starting 17P at 21–26.9 weeks (n = 119) using Fishers exact and Mann–Whitney U test statistics (p < 0.05 considered significant). Results. Mean gestational age at delivery (36.8 ± 3.0 vs. 36.7 ± 2.5) and rates of PTD at <37 weeks (40.4% vs. 48.7%), <35 weeks (16.7% vs. 16.8%) and <32 weeks (5.1% vs. 5.0%) were similar between the groups; all p > 0.05. Conclusions. Rates of preterm delivery were similar in patients initiating 17P at 16–20.9 or 21–26.9 weeks. A larger sample size is warranted in order to confirm our findings.

Perinatal Phosphatidylcholine Supplementation and Early Childhood Behavior Problems: Evidence for CHRNA7 Moderation

OBJECTIVE α7-Nicotinic receptors are involved in the final maturation of GABA inhibitory synapses before birth. Choline at levels found in the amniotic fluid is an agonist at α7-nicotinic receptors. The authors conducted a double-blind placebo-controlled trial to assess whether high-dose oral phosphatidylcholine supplementation during pregnancy to increase maternal amniotic fluid choline levels would enhance fetal development of cerebral inhibition and, as a result, decrease childhood behavior problems associated with later mental illness. METHOD The authors previously reported that newborns in the phosphatidylcholine treatment group have increased suppression of the cerebral evoked response to repeated auditory stimuli. In this follow-up, they report parental assessments of the childrens behavior at 40 months of age, using the Child Behavior Checklist. RESULTS At 40 months, parent ratings of children in the phosphatidylcholine group (N=23) indicated fewer attention problems and less social withdrawal compared with the placebo group (N=26). The improvement is comparable in magnitude to similar deficits at this age associated with later schizophrenia. The childrens behavior is moderated by CHRNA7 variants associated with later mental illness and is related to their enhanced cerebral inhibition as newborns. CONCLUSIONS CHRNA7, the α7-nicotinic acetylcholine receptor gene, has been associated with schizophrenia, autism, and attention deficit hyperactivity disorder. Maternal phosphatidylcholine treatment may, by increasing activation of the α7-nicotinic acetylcholine receptor, alter the development of behavior problems in early childhood that can presage later mental illness.

Consensus Bundle on Maternal Mental Health: Perinatal Depression and Anxiety.

Perinatal mood and anxiety disorders are among the most common mental health conditions encountered by women of reproductive age. When left untreated, perinatal mood and anxiety disorders can have profound adverse effects on women and their children, ranging from increased risk of poor adherence to medical care, exacerbation of medical conditions, loss of interpersonal and financial resources, smoking and substance use, suicide, and infanticide. Perinatal mood and anxiety disorders are associated with increased risks of maternal and infant mortality and morbidity and are recognized as a significant patient safety issue. In 2015, the Council on Patient Safety in Womens Health Care convened an interdisciplinary workgroup to develop an evidence-based patient safety bundle to address maternal mental health. The focus of this bundle is perinatal mood and anxiety disorders. The bundle is modeled after other bundles released by the Council on Patient Safety in Womens Health Care and provides broad direction for incorporating perinatal mood and anxiety disorder screening, intervention, referral, and follow-up into maternity care practice across health care settings. This commentary provides information to assist with bundle implementation.

Maternal deaths from suicide and overdose in Colorado, 2004-2012

OBJECTIVE: To ascertain demographic and clinical characteristics of maternal deaths from self-harm (accidental overdose or suicide) to identify opportunities for prevention. METHODS: We report a case series of pregnancy-associated deaths resulting from self-harm in the state of Colorado between 2004 and 2012. Self-harm deaths were identified from several sources, including death certificates. Birth and death certificates along with coroner, prenatal care, and delivery hospitalization records were abstracted. Descriptive analyses were performed. For context, we describe demographic characteristics of women with a maternal death from self-harm and all women with live births in Colorado. RESULTS: Among the 211 total maternal deaths in Colorado over the study interval, 30% (n=63) resulted from self-harm. The pregnancy-associated death ratio from overdose was 5.0 (95% confidence interval [CI] 3.4–7.2) per 100,000 live births and from suicide 4.6 (95% CI 3.0–6.6) per 100,000 live births. Detailed records were obtained for 94% (n=59) of women with deaths from self-harm. Deaths were equally distributed throughout the first postpartum year (mean 6.21±3.3 months postpartum) with only six maternal deaths during pregnancy. Seventeen percent (n=10) had a known substance use disorder. Prior psychiatric diagnoses were documented in 54% (n=32) and prior suicide attempts in 10% (n=6). Although half (n=27) of the women with deaths from self-harm were noted to be taking psychopharmacotherapy at conception, 48% of them discontinued the medications during pregnancy. Fifty women had toxicology testing available; pharmaceutical opioids were the most common drug identified (n=21). CONCLUSION: Self-harm was the most common cause of pregnancy-associated mortality, with most deaths occurring in the postpartum period. A four-pronged educational and program building effort to include women, health care providers, health care systems, and both governments and organizations at the community and national levels may allow for a reduction in maternal deaths.

Insulin-like growth factor II in gynecological cancers: A preliminary study

PROBLEM: We have previously reported elevated serum levels of cervical human papilloma viral proteins E6 and E7 and serum insulin‐like growth factor II (IGF‐II) in women with cervical cancer and advanced cervical intraepithelial neoplasia. As most women with cervical cancer have elevated levels of serum IGF‐II, we sought to determine whether the cervical cancer and lymph node biopsies from these women demonstrated increased production of IGF‐II and whether this elevation was also present in ovarian and endometrial cancers.

Cortisol during human fetal life: Characterization of a method for processing small quantities of newborn hair from 26 to 42 weeks gestation

OBJECTIVE Fetal cortisol may be reflected in hair collected shortly after birth. The objective of this study was to determine the range of human fetal hair cortisol concentrations (HCC) in live-born neonates using an approach for processing small quantities of hair. MATERIALS AND METHODS Hair was cut on the day of birth from neonates and their mothers, born between 26 and 42 weeks gestational age (GA). HCC was determined by enzyme immunoassay. Maternal sociodemographics and birth data were collected. T-tests, ANOVA, Pearson correlation, and Wilcoxon Signed Rank test were used as appropriate. RESULTS Ninety maternal and neonatal hair samples were cut from 79 term (T) and 11 preterm (PT) delivered pregnancies. All samples weighed ≥2.5 mg. Fetal HCC correlated with GA (r = .25, p = .02) and birth weight (r = .25, p = .03) and was lower in PT (4.3 ± .3 LN pg/mg) than T (5.3 ± .1, LN pg/mg, p < .001) neonates. No significant relationships were seen between fetal HCC and maternal characteristics or maternal HCC. Fetal HCC was significantly higher than maternal HCC. CONCLUSION Fetal cortisol exposure was determined using this approach for processing small amounts of hair. Preterm neonates have significantly lower HCC than term neonates and fetal HCC is associated with GA at delivery and birth weight. Fetal HCC is significantly higher than maternal HCC cut on the same day. These data provide novel information on the intrauterine fetal cortisol environment.

Siglec-6 Expression Is Increased in Placentas From Pregnancies Complicated by Preterm Preeclampsia

Sialic acid immunoglobulin–like lectin (Siglec)-6 is a transmembrane receptor that binds sialyl-TN glycans and leptin. Among eutherian mammals, only human placentas express Siglec-6. Previous work has implicated Siglec-6 in preeclampsia (PE). Preeclampsia, a leading cause of maternal and perinatal morbidity and mortality, is characterized by placental abnormalities. This study provides a comprehensive analysis of Siglec-6 protein expression during human pregnancy by disease state (PE), biologic compartment (basal plate, chorionic villi, or maternal plasma), gestational age (24-41 weeks), and labor status. Siglec-6 protein was increased in both the basal plate and chorionic villi of preterm PE placentas (P < .05). However, expression did not differ at term by disease state, compartment, or labor status. Siglec-6 was not detectable in maternal serum. Overexpression of Siglec-6 protein in preterm PE placentas may contribute to or represent a response to PE pathogenesis and suggests that preterm PE pathogenesis is distinct from term PE.

Placenta percreta masquerading as an acute abdomen.

BACKGROUND: The incidence of placenta percreta has been on the rise during the past decades, coincident with the increase in cesarean deliveries. The diagnosis of this potentially life-threatening complication is difficult, especially when it masquerades as other severe complications of pregnancy. CASE: A woman with one previous cesarean delivery presented at 28 weeks of gestation with right upper quadrant pain. Laparotomy revealed an intraperitoneal hemorrhage from a protrusion of the placenta at the previous uterine incision remote from the site of pain presentation. The fetus was delivered, and a hysterectomy was performed with subsequent good recovery. Pathology confirmed placenta percreta. CONCLUSION: The presentation of an acute abdomen with symptoms remote from the site of pathology in the third trimester masked the diagnosis of placenta accreta. When a clear diagnosis cannot be established, operative exploration must be considered.