Do Maternal Microbes Shape Newborn Oral Microbes?

Strong evidence suggests that the early composition of the oral microbiota of neonates plays an important role for the postnatal development of the oral health or immune system. However, the relationship between the maternal microbiome and the initial neonatal microbiome remains unclear. In this study, 25 pregnant women and their neonates were recruited, and the samples were collected from the maternal oral cavity, amniotic fluid, placenta and neonatal oral cavity. High-throughput sequencing of 16S rRNA was performed using the Illumina MiSeq platform to analyze the correlation with microbial community structure between the maternal and the neonatal oral cavity. The results indicated that the number of shared OTUs was up to 635 in four groups. The PCoA showed that there were certain similarities in the microbial community structure of the four groups. The dominant bacterial genera of the shared OTUs were consistent with human oral microbes, including Streptococcus, Fusobacterium and Prevotella. The results showed that there might be a correlation between the maternal and neonatal oral microbiome, through the amniotic fluid and placenta.Electronic supplementary materialThe online version of this article (10.1007/s12088-020-00901-7) contains supplementary material, which is available to authorized users.     

Effect of Ethiopia’s Health Extension Program on Maternal and Newborn Health Care Practices in 101 Rural Districts: A Dose-Response Study

Background

Improving newborn survival is essential if Ethiopia is to achieve Millennium Development Goal 4. The national Health Extension Program (HEP) includes community-based newborn survival interventions. We report the effect of these interventions on changes in maternal and newborn health care practices between 2008 and 2010 in 101 districts, comprising 11.6 million people, or 16% of Ethiopia’s population.

Methods and Findings

Using data from cross-sectional surveys in December 2008 and December 2010 from a representative sample of 117 communities (kebeles), we estimated the prevalence of maternal and newborn care practices, and a program intensity score in each community. Women with children aged 0 to 11 months reported care practices for their most recent pregnancy and childbirth. The program intensity score ranged between zero and ten and was derived from four outreach activities of the HEP front-line health workers. Dose-response relationships between changes in program intensity and the changes in maternal and newborn health were investigated using regression methods, controlling for secular trend, respondents’ background characteristics, and community-level factors.Between 2008 and 2010, median program intensity score increased 2.4-fold. For every unit increase in the score, the odds of receiving antenatal care increased by 1.13 times (95% CI 1.03–1.23); the odds of birth preparedness increased by 1.31 times (1.19–1.44); the odds of receiving postnatal care increased by 1.60 times (1.34–1.91); and the odds of initiating breastfeeding immediately after birth increased by 1.10 times (1.02–1.20). Program intensity score was not associated with skilled deliveries, nor with some of the other newborn health care indicators.

Conclusions

The results of our analysis suggest that Ethiopia’s HEP platform has improved maternal and newborn health care practices at scale. However, implementation research will be required to address the maternal and newborn care practices that were not influenced by the HEP outreach activities.     

Evaluation of Mineral Concentrations in Maternal Serum Before and After Birth and in Newborn Cord Blood Postpartum—Preliminary Study

The mineral levels in maternal serum change during pregnancy and may be correlated with those of newborn cord blood. The aim of this study was to evaluate the concentrations of calcium (Ca), magnesium (Mg), zinc (Zn), iron (Fe), and copper (Cu) in maternal blood before and after delivery and in umbilical cord vein and artery serum. The study was carried out in 64 Caucasian pregnant women who delivered in a district hospital in Greater Poland region, aged 28.1 ± 5.4 years, with a mean gestational age of 39.2 ± 1.3 weeks. Blood samples were taken from women 2–8 h before delivery and immediately after childbirth. The umbilical cord artery and vein blood of newborns was obtained immediately after childbirth. The levels of minerals in serum were determined by flame atomic absorption spectrometry. A significant drop in the concentrations of Mg (17.71 ± 1.51 vs 17.07 ± 1.61 μg/ml; p < 0.007), Fe (1.08 ± 0.46 vs 0.82 ± 0.35 μg/ml; p < 0.0004), and Zn (0.63 ± 0.17 vs 0.46 ± 0.16; p < 0.0001) in maternal serum was found after delivery. Moreover, higher levels of Ca, Fe, and Zn and lower levels of Cu were observed in the umbilical vein (Ca: 102.80 ± 7.80 μg/ml; p < 0.0001, Fe: 1.96 ± 0.43 μg/ml; p < 0.0001, Zn: 0.65 ± 0.16 μg/ml; p < 0.0001, Cu: 0.36 ± 0.09 μg/ml; p < 0.0001) and in the umbilical artery cord blood (Ca: 98.07 ± 8.18 μg/ml; p < 0.0001, Fe: 1.63 ± 0.30 μg/ml; p < 0.0001, Zn: 0.65 ± 0.15 μg/ml; p < 0.0001, and Cu: 0.36 ± 0.10 μg/ml; p < 0.0001) compared to the maternal serum (Ca: 85.05 ± 10.76 μg/ml, Fe: 0.82 ± 0.35 μg/ml, Zn: 0.46 ± 0.16 μg/ml, and Cu: 1.90 ± 0.35 μg/ml). Fe levels in the cord artery serum negatively correlated with blood loss during delivery (R = ?0.48; p = 0.01), while the Ca concentration in the maternal serum after birth decreased with the age of the women (R = ?0.25; p = 0.03). In conclusion, it seems that the process of birth alters the mineral levels in pregnant women’s blood. Moreover, it was found that blood loss and the age of the mother are associated with mineral concentrations in the maternal serum and cord artery blood.     

Coverage and Financial Risk Protection for Institutional Delivery: How Universal Is Provision of Maternal Health Care in India?

Background

India aims to achieve universal access to institutional delivery. We undertook this study to estimate the universality of institutional delivery care for pregnant women in Haryana state in India. To assess the coverage of institutional delivery, we analyze service coverage (coverage of public sector institutional delivery), population coverage (coverage among different districts and wealth quintiles of the population) and financial risk protection (catastrophic health expenditure and impoverishment as a result of out-of-pocket expenditure for delivery).

Methods

We analyzed cross-sectional data collected from a randomly selected sample of 12,191 women who had delivered a child in the last one year from the date of data collection in Haryana state. Five indicators were calculated to evaluate coverage and financial risk protection for institutional delivery—proportion of public sector deliveries, out-of-pocket expenditure, percentage of women who incurred no expenses, prevalence of catastrophic expenditure for institutional delivery and incidence of impoverishment due to out-of-pocket expenditure for delivery. These indicators were calculated for the public and private sectors for 5 wealth quintiles and 21 districts of the state.

Results

The coverage of institutional delivery in Haryana state was 82%, of which 65% took place in public sector facilities. Approximately 63% of the women reported no expenditure on delivery in the public sector. The mean out-of-pocket expenditures for delivery in the public and private sectors in Haryana were INR 771 (USD 14.2) and INR 12,479 (USD 229), respectively, which were catastrophic for 1.6% and 22% of households, respectively.

Conclusion

Our findings suggest that there is considerably high coverage of institutional delivery care in Haryana state, with significant financial risk protection in the public sector. However, coverage and financial risk protection for institutional delivery vary substantially across districts and among different socio-economic groups and must be strengthened. The success of the public sector in providing high coverage and financial risk protection in maternal health provides encouragement for the role that the public sector can play in universalizing health care.     

Maternal Smoking during Pregnancy and Daughters’ Preeclampsia Risk

Background

An obstetrical paradox is that maternal smoking is protective for the development of preeclampsia. However, there are no prior studies investigating the risk of preeclampsia in women who were exposed to tobacco smoking during their own fetal period. We aimed to study the subsequent risk of preeclampsia in women who were exposed to tobacco smoke in utero, using a national population-based register.

Methods

Data were obtained from the Medical Birth Register of Sweden for women who were born in 1982 (smoking data first recorded) or after, who had given birth to at least one child; 153 885 pregnancies were included.

Results

The associations between intrauterine smoking exposure (three categories: non-smokers, 1–9 cigarettes/day [moderate exposure], and >9 cigarettes/day [heavy exposure]) and subsequent preeclampsia (n = 5721) were assessed using logistic regressions. In models adjusted for maternal age, parity and own smoking, the odds ratios (OR) for preeclampsia were 1.06 [95% CI: 0.99,1.13 for moderate intrauterine exposure, and 1.18, [95% CI: 1.10,1.27] for heavy exposure. Estimates were slightly strengthened in non-smoking women who experienced heavy intrauterine exposure (adjusted OR 1.24 [95% CI: 1.14,1.34]). Results were no longer statistically significant after adjustment for the woman’s own BMI, gestational age and birthweight Z-scores.

Conclusion

These data revealed some evidence of a possible weak positive association between intrauterine smoking exposure and the risk of subsequent preeclampsia, however, results were not significant over all manifestations of preeclampsia and confounder adjustment. The increased risk might be mediated through exposed women’s own BMI or birthweight.     

DRUGS IN PREGNANCY—Their Effects on the Fetus and Newborn

In considering drug therapy for pregnant women, it must be borne in mind that almost all chemical compounds in use as therapeutic agents pass from the maternal to the fetal circulation through the placenta. These drugs can produce a wide range of harmful effects on the fetus and neonatal infant. The effects of some substances for which we have data reflecting a deleterious effect are listed.It is suggested that in the future more caution be exercised in using drugs during pregnancy and that in histories, both obstetrical and pediatric, any therapy given to the mother during gestation be recorded in detail.     

GASTRIC RESECTION—Preoperative and Postoperative Care

Perhaps in no other field of surgery does attention to minute detail play so important a role in determining success as it does in gastric operations.As surgery of the stomach develops toward even greater security and favorable results can be expected with greater confidence, the several aspects of preoperative and postoperative care hitherto regarded as secondary demand closer consideration.     

Do Strategies to Improve Quality of Maternal and Child Health Care in Lower and Middle Income Countries Lead to Improved Outcomes? A Review of the Evidence

Objectives

Efforts to scale-up maternal and child health services in lower and middle income countries will fail if services delivered are not of good quality. Although there is evidence of strategies to increase the quality of health services, less is known about the way these strategies affect health system goals and outcomes. We conducted a systematic review of the literature to examine this relationship.

Methods

We undertook a search of MEDLINE, SCOPUS and CINAHL databases, limiting the results to studies including strategies specifically aimed at improving quality that also reported a measure of quality and at least one indicator related to health system outcomes. Variation in study methodologies prevented further quantitative analysis; instead we present a narrative review of the evidence.

Findings

Methodologically, the quality of evidence was poor, and dominated by studies of individual facilities. Studies relied heavily on service utilisation as a measure of strategy success, which did not always correspond to improved quality. The majority of studies targeted the competency of staff and adequacy of facilities. No strategies addressed distribution systems, public-private partnership or equity. Key themes identified were the conflict between perceptions of patients and clinical measures of quality and the need for holistic approaches to health system interventions.

Conclusion

Existing evidence linking quality improvement strategies to improved MNCH outcomes is extremely limited. Future research would benefit from the inclusion of more appropriate indicators and additional focus on non-facility determinants of health service quality such as health policy, supply distribution, community acceptability and equity of care.     

Are Patents Impeding Medical Care and Innovation?

Background to the debate: Pharmaceutical and medical device manufacturers argue that the current patent system is crucial for stimulating research and development (R&D), leading to new products that improve medical care. The financial return on their investments that is afforded by patent protection, they claim, is an incentive toward innovation and reinvestment into further R&D. But this view has been challenged in recent years. Many commentators argue that patents are stifling biomedical research, for example by preventing researchers from accessing patented materials or methods they need for their studies. Patents have also been blamed for impeding medical care by raising prices of essential medicines, such as antiretroviral drugs, in poor countries. This debate examines whether and how patents are impeding health care and innovation.     

Maternal age and trisomy – a unifying mechanism of formation

The mechanism of trisomy formation and its relationship to increased maternal age is not understood. Molecular analysis of the pattern of inheritance of DNA markers in trisomy families shows trisomies can be grouped according to whether the affected chromosomes inherited from their mothers are heterozygous or homozygous with respect to the centromeres. Furthermore, molecular analysis reveals that those that are heterozygous have fewer chiasmata, which are located more distally, while those that are homozygous have more chiasmata proximally located. Cytogenetic analysis of human oocytes shows that the kind of imbalance predicted by the classic hypothesis of nondisjunction, i.e. extra whole chromosomes at the second metaphase, is rarely found, whereas the common expression of imbalance is seen as single chromatids. We hypothesise that one mechanism links these data: the mechanism depends on the prediction from the cytogenetic data that cohesion within the bivalent complex is severely weakened during the extended dictyate stage in older women. Consequently, when meiosis resumes, at the time of ovulation, the bivalent emerges as four chromatids held together only by its chiasmata. In accordance with the rules of orientation on the spindle, the final balanced shape of the configuration achieved at metaphase I, in this case determined by the position of the chiasmata, will dictate whether the subsequent segregation of the chromatids will result in their heterozygosity or homozygosity. It follows that the concept of "first division" and "second division" errors, i.e. of nondisjunction originating at first or second meiotic division as defined by centromeric hetero- or homozygosity, may be erroneous.     

Differences in Mouse Maternal Care Behavior – Is There a Genetic Impact of the Glucocorticoid Receptor?

Depressive episodes are frequently preceded by stressful life events. Evidence from genetic association studies suggests a role for the glucocorticoid receptor (GR), an essential element in the regulation of stress responses, in the pathophysiology of the disorder. Since the stress response system is affected by pregnancy and postpartum-associated changes, it has also been implicated in the pathophysiology of postpartum depression. Using a 2 × 2 factorial design, we investigated whether a heterozygous deletion of GR would influence maternal care behavior in C57BL/6 and Balb/c mice, two inbred strains known to display qualitative differences in this behavior. Behavioral observation was carried out between postnatal days 1 and 7, followed by a pup retrieval test on postnatal days 7 or 8. While previously noted inter-strain differences were confirmed for different manifestations of caring behavior, self-maintenance and neglecting behaviors as well as the pup retrieval test, no strain-independent effect of the GR mutation was noted. However, an interaction between GR genotype and licking/grooming behavior was observed: it was down-regulated in heterozygous C57BL/6 mice to the level recorded for Balb/c mice. Home cage observation poses minimal disturbance of the dam and her litter as compared to more invasive assessments of dams' emotional behavior. This might be a reason for the absence of any overall effects of the GR mutation, particularly since GR heterozygous animals display a depressive-like phenotype under stressful conditions only. Still, the subtle effect we observed may point towards a role of GR in postpartum affective disorders.     

The differences among Jewish communities—Maternal and paternal contributions

The haplotypes of Y chromosome (paternally inherited) and mtDNA (maternally inherited) were analyzed in representatives of six Jewish communities (Ashkenazic, North African, Near Eastern, Yemenite, Minor Asian/Balkanian, and Ethiopian). For both elements, the Ethiopian community has a mixture of typically African and typically Caucasian haplotypes and is significantly different from all others. The other communities, whose haplotypes are mostly Caucasian, are more closely related; significant differences that were found among some of them possibly indicate the effects of admixture with neighboring communities of non-Jews. The different contribution of the Y chromosome and mtDNA haplotypes to the significant differences among the communities can be explained by unequal involvement of males and females in the different admixtures. In all communities, except the Ethiopians, the level of diversity () for Y chromosome haplotypes is higher than that for mtDNA haplotypes, suggesting that in each community the people who become parents include more males than females. An opposite proportion (more females than males) is found among the Ethiopians. Correspondence to: U. Ritte     

United States Acculturation and Cancer Patients’ End-of-Life Care

Background

Culture shapes how people understand illness and death, but few studies examine whether acculturation influences patients’ end-of-life treatment preferences and medical care.

Methods and Findings

In this multi-site, prospective, longitudinal cohort study of terminally-ill cancer patients and their caregivers (n = 171 dyads), trained interviewers administered the United States Acculturation Scale (USAS). The USAS is a 19-item scale developed to assess the degree of “Americanization” in first generation or non-US born caregivers of terminally-ill cancer patients. We evaluated the internal consistency, concurrent, criterion, and content validity of the USAS. We also examined whether caregivers’ USAS scores predicted patients’ communication, treatment preferences, and end-of-life medical care in multivariable models that corrected for significant confounding influences (e.g. education, country of origin, English proficiency). The USAS measure was internally consistent (Cronbach α = 0.98); and significantly associated with US birthplace (r = 0.66, P<0.0001). USAS scores were predictive of patients’ preferences for prognostic information (AOR = 1.31, 95% CI:1.00–1.72), but not comfort asking physicians’ questions about care (AOR 1.23, 95% CI:0.87–1.73). They predicted patients’ preferences for feeding tubes (AOR = 0.68, 95% CI:0.49–0.99) and wish to avoid dying in an intensive care unit (AOR = 1.36, 95% CI:1.05–1.76). Scores indicating greater acculturation were also associated with increased odds of patient participation in clinical trials (AOR = 2.20, 95% CI:1.28–3.78), compared with lower USAS scores, and greater odds of patients receiving chemotherapy (AOR = 1.59, 95% CI:1.20–2.12).

Conclusion

The USAS is a reliable and valid measure of “Americanization” associated with advanced cancer patients’ end-of-life preferences and care. USAS scores indicating greater caregiver acculturation were associated with increased odds of patient participation in cancer treatment (chemotherapy, clinical trials) compared with lower scores. Future studies should examine the effects of acculturation on end-of-life care to identify patient and provider factors that explain these effects and targets for future interventions to improve care (e.g., by designing more culturally-competent health education materials).     

Maternal–fetal conflict,genomic imprinting and mammalian vulnerabilities to cancer

Antagonistic coevolution between maternal and fetal genes, and between maternally and paternally derived genes may have increased mammalian vulnerability to cancer. Placental trophoblast has evolved to invade maternal tissues and evade structural and immunological constraints on its invasion. These adaptations can be co-opted by cancer in intrasomatic selection. Imprinted genes of maternal and paternal origin favour different degrees of proliferation of particular cell types in which they reside. As a result, the set of genes favouring greater proliferation will be selected to evade controls on cell-cycle progression imposed by the set of genes favouring lesser proliferation. The dynamics of stem cell populations will be a particular focus of this intragenomic conflict. Gene networks that are battlegrounds of intragenomic conflict are expected to be less robust than networks that evolve in the absence of conflict. By these processes, maternal–fetal and intragenomic conflicts may undermine evolved defences against cancer.     

Combined Treatment of Xenon and Hypothermia in Newborn Rats - Additive or Synergistic Effect?

BackgroundBreathing the inert gas Xenon (Xe) enhances hypothermic (HT) neuroprotection after hypoxia-ischemia (HI) in small and large newborn animal models. The underlying mechanism of the enhancement is not yet fully understood, but the combined effect of Xe and HT could either be synergistic (larger than the two effects added) or simply additive. A previously published study, using unilateral carotid ligation followed by hypoxia in seven day old (P7) rats, showed that the combination of mild HT (35°C) and low Xe concentration (20%), both not being neuroprotective alone, had a synergistic effect and was neuroprotective when both were started with a 4 h delay after a moderate HI insult. To examine whether another laboratory could confirm this finding, we repeated key aspects of the study.Design/MethodsAfter the HI-insult 120 pups were exposed to different post-insult treatments: three temperatures (normothermia (NT) NT_37°C, HT_35°C, HT_32°C) or Xe concentrations (0%, 20% or 50%) starting either immediately or with a 4 h delay. To assess the synergistic potency of Xe-HT, a second set (n = 101) of P7 pups were exposed to either HT_35°C+Xe_0%, NT+Xe_20% or a combination of HT_35°C+Xe_20% starting with a 4 h delay after the insult. Brain damage was analyzed using relative hemispheric (ligated side/unligated side) brain tissue area loss after seven day survival.ResultsImmediate HT_32°C (p = 0.042), but not HT_35°C significantly reduced brain injury compared to NT_37°C. As previously shown, adding immediate Xe_50% to HT_32°C increased protection. Neither 4 h-delayed Xe_20%, nor Xe_50% at 37°C significantly reduced brain injury (p>0.050). In addition, neither 4 h-delayed HT_35°C alone, nor HT_35°C+Xe_20% reduced brain injury. We found no synergistic effect of the combined treatments in this experimental model.ConclusionsCombining two treatments that individually were ineffective (delayed HT_35°C and delayed Xe_20%) did not exert neuroprotection when combined, and therefore did not show a synergistic treatment effect.     

Ethnic Elders and American Health Care—A Physician's Perspective

The aging process is a fugue composed of innumerable themes; the theme of “ethnicity” is by far one of its more dominant. Due to the increasing incidence of chronic, progressive infirmity and acute, catastrophic illness, the elderly are thrust into direct contact with the health care systems of their society. The experiences of ethnic elders in American health care situations are fraught with conflict and mutual dissatisfaction with the physician-patient relationship. Both providers and consumers of health care services harbor differing culture-bound perceptions of health, illness and the healing process; these cultural beliefs define personal and professional needs and expectations and notions of how those needs are to be met by others. Both physicians and patients can enhance their communication and their compassion for one another by acknowledgment of cultural differences and by increased willingness to interpret motives and behavior within native context.It behooves us in medicine to examine the cultural traditions underlying our own attitudes, beliefs and values about the aged in a universal sense, as well as in a culturally specific sense, that we may gain insight that will be helpful in serving elderly persons more effectively, and in solving some of the problems inherent in the aging process.     

Maternal inflammatory diet and adverse pregnancy outcomes: Circulating cytokines and genomic imprinting as potential regulators?

Excessive inflammation during pregnancy alters homeostatic mechanisms of the developing fetus and has been linked to adverse pregnancy outcomes. An anti-inflammatory diet could be a promising avenue to combat the pro-inflammatory state of pregnancy, particularly in obese women, but we lack mechanistic data linking this dietary pattern during pregnancy to inflammation and birth outcomes. In an ethnically diverse cohort of 1057 mother-child pairs, we estimated the relationships between dietary inflammatory potential [measured via the energy-adjusted dietary inflammatory index (E-DII?)] and birth outcomes overall, as well as by offspring sex and maternal pre-pregnancy body mass index (BMI). In a subset of women, we also explored associations between E-DII, circulating cytokines (n = 105), and offspring methylation (n = 338) as potential modulators of these relationships using linear regression. Adjusted regression models revealed that women with pro-inflammatory diets had elevated rates of preterm birth among female offspring [β = ?0.22, standard error (SE) = 0.07, P<0.01], but not male offspring (β=0.09, SE = 0.06, P<0.12) (P_interaction = 0.003). Similarly, we observed pro-inflammatory diets were associated with higher rates of caesarean delivery among obese women (β = 0.17, SE = 0.08, P = 0.03), but not among women with BMI <25 kg/m² (P_interaction = 0.02). We observed consistent inverse associations between maternal inflammatory cytokine concentrations (IL-12, IL-17, IL-4, IL-6, and TNFα) and lower methylation at the MEG3 regulatory sequence (P<0.05); however, results did not support the link between maternal E-DII and circulating cytokines. We replicate work by others on the association between maternal inflammatory diet and adverse pregnancy outcomes and provide the first empirical evidence supporting the inverse association between circulating cytokine concentrations and offspring methylation.