Mona Prasad

The clinical content of preconception care: women with chronic medical conditions.

This article reviews the medical conditions that are associated with adverse pregnancy outcomes for women and their offspring. We also present the degree to which specific preconception interventions and treatments can impact the effects of the condition on birth outcomes. Because avoiding, delaying, or achieving optimal timing of a pregnancy is often an important component of the preconception care of women with medical conditions, contraceptive considerations particular to the medical conditions are also presented.

Hepatitis C virus in pregnancy.

Despite recent advances in the pathogenesis, treatment, and public health response to hepatitis C virus (HCV), HCV as it specifically relates to pregnancy has been a neglected condition. HCV-monoinfected pregnant women have a 2-8% risk of viral transmission to their infant, but the mechanism and timing of mother to child transmission (MTCT) are not fully understood, nor is the natural history of the illness in pregnant women and their offspring. Recognition of HCV-infected pregnant women is relevant because of the long-term health implications for the mother, potential adverse effects of infection on pregnancy outcomes, and the possibility of transmission to their infants. Certain risk factors for MTCT of HCV appear similar to those for human immunodeficiency virus (HIV); however, unlike HIV, effective methods for prevention of HCV vertical transmission have not been developed. It is possible that a better understanding of HCV MTCT and pathogenesis in pregnancy will guide development of useful prevention strategies, particularly as we enter an era where interferon-free drug cocktails may emerge as viable treatment options for HCV.

High-dose methadone in pregnant women and its effect on duration of neonatal abstinence syndrome

OBJECTIVE The purpose of this study was to examine high-dose methadone in pregnant women and its effect on the duration of neonatal abstinence syndrome. STUDY DESIGN This was a retrospective chart review of 68 neonates and their mothers who received methadone therapy during pregnancy. The last dosage of maternal methadone just before delivery and the length of treatment for neonatal abstinence syndrome were examined with an analysis of variance model. RESULTS When the data were analyzed for methadone dosages as a continuous variable, each 1-mg increase in the last maternal methadone dosage before delivery was associated with an additional 0.18 days of infant treatment for neonatal abstinence syndrome (P < .001; 95% CI, 0.112-0.255). In other words, every increase of 5.5 mg of methadone in the mother was associated statistically with 1 additional day of neonatal abstinence syndrome treatment for the infant. Gestational age at delivery and birthweight were not statistically significant. CONCLUSION Higher doses of maternal methadone were associated with an increase in diagnosis and longer duration of neonatal abstinence syndrome.

Loss of immune escape mutations during persistent HCV infection in pregnancy enhances replication of vertically transmitted viruses

Globally, about 1% of pregnant women are persistently infected with the hepatitis C virus (HCV). Mother-to-child transmission of HCV occurs in 3–5% of pregnancies and accounts for most new childhood infections. HCV-specific CD8+ cytotoxic T lymphocytes (CTLs) are vital in the clearance of acute HCV infections, but in the 60–80% of infections that persist, these cells become functionally exhausted or select for mutant viruses that escape T cell recognition. Increased HCV replication during pregnancy suggests that maternofetal immune tolerance mechanisms may further impair HCV-specific CTLs, limiting their selective pressure on persistent viruses. To assess this possibility, we characterized circulating viral quasispecies during and after consecutive pregnancies in two women. This revealed a loss of some escape mutations in HLA class I epitopes during pregnancy that was associated with emergence of more fit viruses. CTL selective pressure was reimposed after childbirth, at which point escape mutations in these epitopes again predominated in the quasispecies and viral load dropped sharply. Importantly, the viruses transmitted perinatally were those with enhanced fitness due to reversion of escape mutations. Our findings indicate that the immunoregulatory changes of pregnancy reduce CTL selective pressure on HCV class I epitopes, thereby facilitating vertical transmission of viruses with optimized replicative fitness.

The clinical content of preconception care: infectious diseases in preconception care.

A number of infectious diseases should be considered for inclusion as part of clinical preconception care. Those infections strongly recommended for health promotion messages and risk assessment or for the initiation of interventions include Chlamydia infection, syphilis, and HIV. For selected populations, the inclusion of interventions for tuberculosis, gonorrheal infection, and herpes simplex virus are recommended. No clear evidence exists for the specific inclusion in preconception care of hepatitis C, toxoplasmosis, cytomegalovirus, listeriosis, malaria, periodontal disease, and bacterial vaginosis (in those with a previous preterm birth). Some infections that have important consequences during pregnancy, such as bacterial vaginosis (in those with no history of preterm birth), asymptomatic bacteriuria, parvovirus, and group B streptococcus infection, most likely would not be improved through intervention in the preconception time frame.

Association of the duration of active pushing with obstetric outcomes

OBJECTIVE: To estimate the associations between the duration of active pushing during the second stage of labor and maternal and neonatal outcomes. METHODS: We performed an observational study in which data were obtained by trained abstractors from maternal and neonatal charts of deliveries at 25 hospitals over a 3-year period. In this secondary analysis, women with no prior cesarean delivery who had a term, singleton, cephalic gestation and reached complete dilation were analyzed. The duration of pushing, defined as the time from initiation of pushing to either vaginal delivery or the decision to proceed with a cesarean delivery, was determined. The primary maternal outcome was cesarean delivery and the primary neonatal outcome was a composite that included: mechanical ventilation, proven sepsis, brachial plexus palsy, clavicular fracture, skull fracture, other fracture, seizures, hypoxic–ischemic encephalopathy, or death. Nulliparous and parous women were analyzed separately in univariable and then multivariable analyses. RESULTS: A total of 53,285 women were analyzed. In both nulliparous and parous women, longer duration of pushing was associated with increased odds of both cesarean delivery and the neonatal adverse outcome composite. Nevertheless, even after 4 hours of pushing, approximately 78% of nulliparous women who continued with active pushing had a vaginal delivery and more than 97% did not have the composite adverse neonatal outcome. Similarly, after more than 2 hours of pushing, approximately 82% of parous women who continued active pushing delivered vaginally and more than 97% did not have the adverse neonatal outcome. CONCLUSION: A longer duration of pushing is associated with an increased relative risk, but small absolute difference in risk, of neonatal complications. Approximately 78% of nulliparous women delivered vaginally even after 4 hours of pushing.

Evaluating the concerns of pregnant women with epilepsy: A focus group approach

RATIONALE Some women with epilepsy stop or decrease their antiepileptic drug (AED) therapy during pregnancy because they fear fetal effects of the therapy. This places the patient and her fetus at risk for potential adverse outcomes due to increased seizure activity. The rationale of this behavior is not completely understood and is underexplored. The aim of this qualitative project was to determine the concerns of pregnant women with epilepsy via small focus groups. METHODS Pregnant women with epilepsy were recruited to participate in small group sessions involving direct interviews which were analyzed by thematic content analysis. RESULTS Ten focus groups were conducted with a total of 21 second or third trimester pregnant women with epilepsy. Twelve women reported changes to their AED regimen during pregnancy, with six having made changes requested by their prescriber and six (29% of all study participants) self-altering their AED regimen. In contrast to the former group, the alterations made by the latter group were either dose-lowering or stopping AEDs altogether. Via content analysis, four pregnancy specific patient-related concerns arose: 1) the safety of drug therapy during pregnancy, 2) potential neonatal complications, 3) labor and delivery issues and 4) neonatal and post-partum management. An unanticipated benefit was the fostering of patient comfort and an opportunity for patient-to-patient collaboration. CONCLUSIONS Our study adds insight into the concerns of pregnant women with epilepsy. By identifying these concerns, we may be able to provide more effective patient education, and we hope to ultimately improve outcomes in women with epilepsy.

Obstetric and neonatal outcomes of cancer treated during pregnancy

Cancer diagnosed during pregnancy is a rare occurrence with an incidence of 0.1% of all pregnancies. However, its management can be challenging at times as one balances maternal benefit to fetal risk. Various treatment modalities are used in this context including surgical intervention, chemotherapy, and radiologic therapy. This review seeks to address the impact of pregnancy on disease as well as the effect of malignancy and its treatment on both mother and fetus. Attention is focused on the more common malignancies associated with pregnancy: cervix, breast, melanoma, and hematologic malignancies. In addition, special emphasis is placed on timing of delivery and how that affects neonatal outcomes.

Prolonged activation of innate antiviral gene signature after childbirth is determined by IFNL3 genotype.

Significance In this study, we examined the possibility that the maternal innate immune system is modulated following delivery. We identified an interferon-stimulated gene signature that was primarily expressed in CD14+ cells circulating in the peripheral blood. Postpartum antiviral gene expression depended on the interferon-λ3 (IFNL3) single-nucleotide polymorphism rs12979860, which suggests that IFNL3 genotype may influence a mother’s innate immune response following delivery. Maternal innate and adaptive immune responses are modulated during pregnancy to concurrently defend against infection and tolerate the semiallogeneic fetus. The restoration of these systems after childbirth is poorly understood. We reasoned that enhanced innate immune activation may extend beyond gestation while adaptive immunity recovers. To test this hypothesis, the transcriptional profiles of total peripheral blood mononuclear cells following delivery in healthy women were compared with those of nonpregnant control subjects. Interestingly, interferon-stimulated genes (ISGs) encoding proteins such as IFIT1, IFIT2, and IFIT3, as well as signaling proteins such as STAT1, STAT2, and MAVS, were enriched postpartum. Antiviral genes were primarily expressed in CD14+ cells and could be stratified according to genetic variation at the interferon-λ3 gene (IFNL3, also named IL28B) SNP rs12979860. Antiviral gene expression was sustained beyond 6 mo following delivery in mothers with a CT or TT genotype, but resembled baseline nonpregnant control levels following delivery in mothers with a CC genotype. CT and TT IFNL3 genotypes have been associated with persistent elevated ISG expression in individuals chronically infected with hepatitis C virus. Together, these data suggest that postpartum, the normalization of the physiological rheostat controlling IFN signaling depends on IFNL3 genotype.

Neonatal Morbidity of Small- and Large-for-gestational-age Neonates Born at Term in Uncomplicated Pregnancies

OBJECTIVE To compare morbidity among small-for-gestational-age (SGA; birth weight less than the 10th percentile for gestational age), appropriate-for-gestational-age (AGA; birth weight 10th to 90th percentile; reference group), and large-for-gestational-age (LGA; birth weight greater than the 90th percentile) neonates in apparently uncomplicated pregnancies at term (37 weeks of gestation or greater). METHODS This secondary analysis, derived from an observational obstetric cohort of 115,502 deliveries, included women with apparently uncomplicated pregnancies of nonanomalous singletons who had confirmatory ultrasound dating no later than the second trimester and who delivered between 37 0/7 and 42 6/7 weeks of gestation. We used two different composite neonatal morbidity outcomes: hypoxic composite neonatal morbidity for SGA and traumatic composite neonatal morbidity for LGA neonates. Log Poisson relative risks (RRs) with 95% CIs adjusted for potential confounding factors (nulliparity, body mass index, insurance status, and neonatal sex) were calculated. RESULTS Among the 63,436 women who met our inclusion criteria, SGA occurred in 7.9% (n=4,983) and LGA in 8.3% (n=5,253). Hypoxic composite neonatal morbidity was significantly higher in SGA (1.1%) compared with AGA (0.7%; adjusted RR 1.44, 95% CI 1.07-1.93) but similar between LGA (0.6%) and AGA (adjusted RR 0.84, 95% CI 0.58-1.22). Traumatic composite neonatal morbidity was significantly higher in LGA (1.9%) than AGA (1.0%; adjusted RR 1.88, 95% CI 1.51-2.34) but similar in SGA (1.3%) compared with AGA (adjusted RR 1.28, 95% CI 0.98-1.67). CONCLUSION Among women with uncomplicated pregnancies, hypoxic composite neonatal morbidity is more common with SGA neonates and traumatic-composite neonatal morbidity is more common with LGA neonates.