Abstract P230: Prevention Of Maternal Obesity Attenuates Adverse Offspring Cardiometabolic Outcomes In Preeclamptic-like Mouse Model

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Kalie Beckers ◽  
Juliet Flanagan ◽  
Viviane Gomes ◽  
ChinCHi Liu ◽  
Andrea Johnston ◽  
...  
Keyword(s):  
Inflammatory Cytokine ◽  
Cardiometabolic Risk ◽  
Maternal Obesity ◽  
Fold Increase ◽  
Female Offspring ◽  
Fetal Mortality ◽  
Hypertensive Disorder ◽  
Dependent Manner ◽  
Daily Food ◽  
Similar Body

Preeclampsia (PE) is a hypertensive disorder of pregnancy and a leading cause of maternal and fetal mortality with maternal obesity as a risk factor. Decreasing white adipose tissue (WAT) via calorie restriction during the first half of pregnancy may alter the maternal-fetal environment to improve offspring outcomes. We hypothesized that pair-feeding BPH/5 dams during pregnancy will improve cardiometabolic risk and WAT pro-inflammatory cytokine expression in BPH/5 offspring in a sex-dependent manner. Previously, we showed that BPH/5 males, unlike females, have similar body weights, daily food intake, and circulating leptin levels as compared to age-matched control mice. Although, adult BPH/5 females and males have cardiomegaly and increased subcutaneous and peri-renal WAT mass compared to lean control mice. To investigate the prevention of maternal obesity on offspring outcomes, BPH/5 dams were pair-fed (PF) beginning at embryonic day (e)0.5 to C57 pregnant mice. Offspring cardiometabolic risk and WAT pro-inflammatory cytokine mRNA were measured using real time PCR in adult ad libitum fed offspring. Compared to controls, peri-renal WAT from BPH/5 males showed a 5-fold increase while females had a 15-fold increase in TNFa (n=3-6; p<0.05), 6-fold increase in PTGS-2 for males and 5-fold increase for females (n=3-6; p<0.05), and 3-fold increase in IL-6 for males and 1.25-fold increase for females (n=3-6; p<0.05) in subcutaneous WAT. Adult offspring born to PF BPH/5 dams had decreased expression in TNFa (male: 4-fold and female: 7-fold), PTGS-2 (male: 5-fold and female: 4-fold), and IL-6 (male: 10-fold; n=3-6; p<0.05). In conclusion, prevention of maternal obesity in BPH/5 dams attenuates cardiometabolic risks and reduces the pro-inflammatory WAT milieu in male and female offspring. The transgenerational effects during pregnancy is believed to be caused by an alteration in the maternal-fetal environment due to WAT pro-inflammatory adipokines. Future investigations are necessary to understand the differences observed in BPH/5 male versus female mice into adulthood as well as the transgenerational impact of attenuated maternal obesity in pregnancy.

scholarly journals Cardiometabolic Phenotypic Differences in Male Offspring Born to Obese Preeclamptic-Like BPH/5 Mice

2021 ◽  
Vol 9 ◽  
Author(s):  
Kalie F. Beckers ◽  
Viviane C. L. Gomes ◽  
Kassandra J. Raven Crissman ◽  
Daniella M. Adams ◽  
Chin-Chi Liu ◽  
...  
Keyword(s):  
Adult Male ◽  
Maternal Obesity ◽  
Gestational Hypertension ◽  
Female Offspring ◽  
Left Ventricular ◽  
Male Offspring ◽  
Hypertensive Disorder ◽  
Male And Female ◽  
Similar Body ◽  
The Impact

Preeclampsia (PE) is a hypertensive disorder of pregnancy occurring in approximately 10% of women worldwide. While it is life threatening to both the mother and baby, the only effective treatment is delivery of the placenta and fetus, which is often preterm. Maternal obesity is a risk factor for PE, and the effects of both on offspring are long standing with increased incidence of cardiometabolic disease in adulthood. Obese BPH/5 mice spontaneously exhibit excessive gestational weight gain and late-gestational hypertension, similar to women with PE, along with fetal growth restriction and accelerated compensatory growth in female offspring. We hypothesized that BPH/5 male offspring will demonstrate cardiovascular and metabolic phenotypes similar to BPH/5 females. As previously described, BPH/5 females born to ad libitum-fed dams are overweight with hyperphagia and increased subcutaneous, peri-renal, and peri-gonadal white adipose tissue (WAT) and cardiomegaly compared to age-matched adult female controls. In this study, BPH/5 adult male mice have similar body weights and food intake compared to age-matched control mice but have increased inflammatory subcutaneous and peri-renal WAT and signs of cardiovascular disease: left ventricular hypertrophy and hypertension. Therefore, adult male BPH/5 do not completely phenocopy the cardiometabolic profile of female BPH/5 mice. Future investigations are necessary to understand the differences observed in BPH/5 male and female mice as they age. In conclusion, the impact of fetal programming due to PE has a transgenerational effect on both male and female offspring in the BPH/5 mouse model. The maternal obesogenic environment may play a role in PE pregnancy outcomes, including offspring health as they age.

Abstract P217: Phenotypic Difference Exist Between Bph/5 Offspring In A Sex-dependent Manner

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Kalie Beckers ◽  
Viviane Gomes ◽  
Kat Robillard ◽  
Chin-CHi Liu ◽  
Andrea Johnston ◽  
...  
Keyword(s):  
Maternal Obesity ◽  
Gestational Hypertension ◽  
Female Offspring ◽  
Hypertensive Disorder ◽  
Dependent Manner ◽  
Obesogenic Environment ◽  
Maternal Weight ◽  
Phenotypic Analysis ◽  
Phenotypic Differences ◽  
In Pregnancy

Preeclampsia (PE) is a hypertensive disorder of pregnancy occurring in ~10% of women worldwide. Maternal obesity is a risk factor for PE and the effects on offspring are long-standing with increased incidence of cardiometabolic disease into adulthood. The maternal obesogenic environment may play a role in pregnancy outcomes and offspring in a sex-dependent manner; however, in the context of superimposed PE, it is not completely understood. Obese BPH/5 mice spontaneously exhibit late-gestational hypertension, fetal demise and growth restriction, and excessive gestational weight gain, similar to PE. We hypothesized that phenotypic differences exist between female and male BPH/5 offspring and maternal weight loss in BPH/5 during pregnancy would influence these phenotypic differences. Obese BPH/5 dams were calorie restricted via pair-feeding (PF) to match the food intake of C57 dams for the first 9 days of pregnancy. Offspring were fed an ad libitum (lib) diet until phenotypic analysis. Body weights (BW), visceral peri-gonadal and peri-renal white adipose tissue (WAT), hearts, and livers were recorded in BPH/5 and control C57 age-matched adult females and males born to ad lib fed and PF dams. Values are reported as mean ± standard error of the mean. As previously described, BPH/5 females born to ad lib fed dams are overweight with increased peri-renal and gonadal WAT, cardiomegaly, and hepatomegaly (1308 ±13.3 vs 979.9 ±82.3g in C57, p<0.05). BPH/5 male mice are underweight (23.8±1.6 vs C57: 27.9±1.6g) with increased peri-renal WAT (158± 23 vs C57: 53.25±10.3mg, p<0.05), and cardiomegaly (heart: BW 8.1±0.5 vs C57: 5.7±1.1, p<0.05). Without altering BPH/5 male or female offspring BW, peri-renal adiposity (males: 103.5±13mg, females: 73.2±10.3mg, p<0.05), cardiomegaly (males: 5.74±0.5, females: 6.03±0.4, p<0.05), and female hepatomegaly (1149.8 ±58.1mg, p<0.05) are significantly attenuated in PF BPH/5 dams. To conclude, reduction in the maternal obesogenic environment may play a role in BPH/5 sex-dependent phenotypic differences. Future investigations are necessary to understand the differences observed in BPH/5 male versus female mice into adulthood as well as the transgenerational impact of attenuated maternal obesity in pregnancy.

scholarly journals Maternal metabolic syndrome induces liver injury and promotes tumor growth in the offspring

2021 ◽  
Vol 108 (Supplement_4) ◽  
Author(s):  
B Moeckli ◽  
V Delaune ◽  
A Peloso ◽  
L Orci ◽  
F Slits ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Gut Microbiome ◽  
Disease Transmission ◽  
Maternal Obesity ◽  
Female Offspring ◽  
Normal Diet ◽  
Reproductive Age ◽  
Standard Diet ◽  
Dependent Manner ◽  
Alcoholic Fatty Liver

Abstract Objective Obesity is a growing disease entity affecting a third of women of reproductive age. Epidemiological studies show that children of obese mothers suffer from obesity, long-term morbidity and an increased rate of childhood cancers. However, the mechanisms of disease transmission remain unknown. The aim of this study is to test this hypothesis in a mouse model and shed light on the involved mechanisms of vertical transmission. Methods Female mice were fed a high fat or standard diet (HFD/SD) for 16 weeks before being mated with mice fed a normal diet. Corresponding diet was continued until weaning, all offspring were thereafter fed a SD. Metabolic profile, weight gain, liver enzymes and the gut microbiota profile were assessed in the offspring (n = 24). Additional groups of offspring (n = 48) were injected with a carcinogen (diethylnitrosamine) at week two, tumor characteristics were assessed by computed tomography scan at week 36. Results Mothers fed HFD developed obesity and non-alcoholic fatty liver disease (NAFLD). Female offspring of mothers fed HFD gained significantly more weight (+33.7%, p = 0.001), had increased alanine transaminase levels (62 vs 18 IU/L, p = 0.003) and a significantly altered liver histology exemplified by an increased NAFLD activity score (3.8 vs 0.6, p = 0.016). Expression levels of several candidate genes were studied of which FGF21 showed the largest differential expression between HFD and SD offspring (9 vs 1 2^ΔΔCT, p = &lt;0.001). However, epigenetic analysis of FGF21 in the liver revealed no changes in methylation level between HFD and SD offspring. Furthermore, offspring of HFD mothers had a distinctly altered gut microbiome with lower proportions of Bacteroides caccae, Bacteroidales and Parasutterella excrementihominis. Interestingly, the proportion of female offspring developing tumors was significantly higher in offspring of HFD mothers (83 vs 44%, p = 0.011), the average total tumor volume was larger (234 vs 3.5mm3, p = 0.022) and the offspring developed more tumors (3.5 vs 0.6, p = 0.010). Conclusion Maternal obesity promotes liver tumor growth in the offspring, alters metabolic patterns and induces liver suffering in the progeny in a sex-dependent manner. The gut microbiome seems to play a role in this transmission of disease. Yet further research is needed to determine the vectors of transmission and evaluate preventive interventions in obese mothers.

scholarly journals HYBID (alias KIAA1199/CEMIP) and hyaluronan synthase coordinately regulate hyaluronan metabolism in histamine-stimulated skin fibroblasts

2020 ◽  
Vol 295 (8) ◽  
pp. 2483-2494
Author(s):  
Hiroyuki Yoshida ◽  
Mika Aoki ◽  
Aya Komiya ◽  
Yoko Endo ◽  
Keigo Kawabata ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Fold Increase ◽  
Histamine Receptor ◽  
Skin Fibroblasts ◽  
Dependent Manner ◽  
Skin Damage ◽  
Photoaged Skin ◽  
Molecular Sizes ◽  
Ha Synthase ◽  
Hyaluronan Binding

The immune-regulatory compound histamine is involved in the metabolism of the essential skin component hyaluronan (HA). We previously reported that histamine up-regulates the expression of HYBID (hyaluronan-binding protein involved in hyaluronan depolymerization, also called CEMIP or KIAA1199), which plays a key role in HA degradation. However, no information is available about histamine's effects on HA synthase (HAS) expression, the molecular sizes of HA species produced, and histamine receptors and their signaling pathways in skin fibroblasts. Moreover, histamine's effects on photoaged skin remain elusive. Here, we show that histamine increases HA degradation by up-regulating HYBID and down-regulating HAS2 in human skin fibroblasts in a dose- and time-dependent manner and thereby decreases the total amounts and sizes of newly produced HA. Histamine H1 blocker abrogated the histamine effects on HYBID up-regulation, HAS2 suppression, and HA degradation. Histamine H1 agonist exhibited effects on HA levels, composition, and breakdown similar to those of histamine. Of note, blockade of protein kinase Cδ or PI3K–Akt signaling abolished histamine-mediated HYBID stimulation and HAS2 suppression, respectively. Immunohistochemical experiments revealed a significant ∼2-fold increase in tryptase-positive mast cells in photoaged skin, where HYBID and HAS2 expression levels were increased and decreased, respectively, compared with photoprotected skin. These results indicate that histamine controls HA metabolism by up-regulating HYBID and down-regulating HAS2 via distinct signaling pathways downstream of histamine receptor H1. They further suggest that histamine may contribute to photoaged skin damage by skewing HA metabolism toward degradation.

scholarly journals Prognostic value of different maternal obesity phenotypes in predicting offspring obesity in a family-based cohort study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sara Jalali-Farahani ◽  
Parisa Amiri ◽  
Bita Lashkari ◽  
Leila Cheraghi ◽  
Farhad Hosseinpanah ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Childhood Obesity ◽  
Maternal Obesity ◽  
Female Offspring ◽  
Normal Weight ◽  
Metabolic Status ◽  
World Health ◽  
Metabolic Phenotype ◽  
Maternal Body Mass Index ◽  
Obesity In Children

Abstract Background Parental weight is studied as an important determinant of childhood obesity; however, obesity-related metabolic abnormalities have been less considered as determinants of childhood obesity. This study aimed to investigate the association between maternal obesity phenotypes and incidence of obesity in their offspring. Methods This longitudinal study was conducted within the framework of the Tehran Lipid and Glucose Study. A total of 2151 non-obese children who had complete parental information were followed for incidence of obesity over a mean of 148.7 ± 34.7 months. Obesity in children was defined using the World Health Organization criteria. Maternal body mass index (BMI) was classified into three categories: normal weight, overweight and obese. Dysmetabolic status was considered as having metabolic syndrome or diabetes. Metabolic syndrome and diabetes were defined according to the Joint Interim Statement and American diabetes association criteria, respectively. Considering maternal BMI categories and metabolic status, six obesity phenotypes were defined as followed: 1) normal weight and normal metabolic status, 2) overweight and normal metabolic status, 3) obese and normal metabolic status, 4) normal weight and dysmetabolic status, 5) overweight and dysmetabolic status, and 6) obese and dysmetabolic status. The association between maternal obesity phenotypes and incidence of obesity in children was studied using Cox proportional regression hazard model. Results In male offspring, the risk of incidence of obesity significantly increased in those with maternal obesity phenotypes including overweight/normal metabolic: 1.75(95% CI: 1.10–2.79), obese/normal metabolic: 2.60(95%CI: 1.51–4.48), overweight/dysmetabolic: 2.34(95%CI: 1.35–4.03) and obese/dysmetabolic: 3.21(95%CI: 1.94–5.03) compared to the normal weight/normal metabolic phenotype. Similarly, in girls, the risk of incidence of obesity significantly increased in offspring with maternal obesity phenotypes including overweight/normal metabolic: 2.39(95%CI: 1.46–3.90), obese/normal metabolic: 3.55(95%CI: 1.94–6.46), overweight/dysmetabolic: 1.92(95%CI: 1.04–3.52) and obese/dysmetabolic: 3.89(95%CI: 2.28–6.64) compared to normal weight/normal metabolic phenotype. However, maternal normal weight/dysmetabolic phenotype did not significantly change the risk of obesity in both male and female offspring. Conclusion Except for normal weight/dysmetabolic phenotype, all maternal obesity phenotypes had significant prognostic values for incidence of offspring obesity with the highest risk for obese/dysmetabolic phenotype. This study provides valuable findings for identifying the first line target groups for planning interventions to prevent childhood obesity.

scholarly journals Gestation Food Restriction and Refeeding Compensate Maternal Energy Status and Alleviate Metabolic Consequences in Juvenile Offspring in a Rabbit Model

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 310
Author(s):  
Rosa M. García-García ◽  
María Arias-Álvarez ◽  
Pilar Millán ◽  
María Rodríguez ◽  
Ana Sánchez-Rodríguez ◽  
...  
Keyword(s):  
Food Restriction ◽  
Rabbit Model ◽  
Later Life ◽  
Female Offspring ◽  
Energy Status ◽  
Juvenile Period ◽  
Body Reserves ◽  
Effect Of Food ◽  
Serum Aminotransferases ◽  
Similar Body

Nutritional status during gestation can influence mother and offspring metabolism. Undernutrition in pregnancy affects women in both western and developing countries, and it is associated with a high prevalence of chronic diseases in later life. The present work was conducted in the rabbit model, as a longitudinal study, to examine the effect of food restriction during early and mid-gestation, and re-feeding ad libitum until the end of pregnancy on metabolic status and body reserves of mother and, its association with development and metabolism of fetuses and female offspring to the juvenile stage. Little changes in live body weight (LBW), compensatory feed intake, similar body reserves, and metabolism were observed in dams. Placenta biometry and efficiency were slightly affected, but fetal BW and phenotype were not modified. However, hyperinsulinemia, insulin resistance, and hypertriglyceridemia were demonstrated in pre-term fetuses. In the juvenile period, these changes were not evidenced, and a similar pattern of growth and serum metabolic parameters in offspring of food-restricted mothers were found, except in serum aminotransferases levels, which increased. These were associated with higher liver fibrosis. Maternal food restriction in the early and mid-pregnancy followed by re-feeding in our rabbit model established a compensatory energy status in dams and alleviated potential long-term consequences in growth and metabolism in the offspring, even if fetal metabolism was altered.

Tamoxifen inhibits phorbol ester stimulated osteoclastic bone resorption: An effect mediated by calmodulin

2000 ◽  
Vol 78 (6) ◽  
pp. 715-723 ◽  
Author(s):  
John P Williams ◽  
Margaret A McKenna ◽  
Allyn M Thames III ◽  
Jay M McDonald
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Bone Resorption ◽  
Phorbol Ester ◽  
Phorbol Esters ◽  
Fold Increase ◽  
Dependent Manner ◽  
Osteoclast Activity ◽  
Kinase C ◽  
Protein Kinase Cα

Tamoxifen inhibits bone resorption by disrupting calmodulin-dependent processes. Since tamoxifen inhibits protein kinase C in other cells, we compared the effects of tamoxifen and the phorbol ester, phorbol myristate acetate, on osteoclast activity. Phorbol esters stimulate bone resorption and calmodulin levels four-fold (k0.5 = 0.1–0.3 µM). In contrast, tamoxifen inhibited osteoclast activity ~60% with an IC50 of 1.5 µM, had no apparent effect on protein kinase C activity in whole-cell lysates, and reduced protein kinase Cα recovered by immunoprecipitation 75%. Phorbol esters stimulated resorption in a time-dependent manner that was closely correlated with a similar-fold increase in calmodulin. Protein kinase Cα, β, δ, ε, and ζ were all down-regulated in response to phorbol ester treatment. Tamoxifen and trifluoperazine inhibited PMA-dependent increases in bone resorption and calmodulin by 85 ± 10%. Down-regulation of protein kinase C isoforms by phorbol esters suggests that the observed increases in bone resorption and calmodulin levels are most likely due to a mechanism independent of protein kinase C and dependent on calmodulin. In conclusion, the data suggest that protein kinase C negatively regulates calmodulin expression and support the hypothesis that the effects of both phorbol esters and tamoxifen on osteoclast activity is mediated by calmodulin.Key words: osteoclast, calmodulin, tamoxifen, osteoporosis, protein kinase C.

Candida tropicalis induces pro-inflammatory cytokine production, NF-κB and MAPKs pathways regulation, and dectin-1 activation

2018 ◽  
Vol 64 (12) ◽  
pp. 937-944 ◽  
Author(s):  
Zhimin Duan ◽  
Qing Chen ◽  
Rong Zeng ◽  
Leilei Du ◽  
Caixia Liu ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Inflammatory Cytokine ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Downstream Signaling ◽  
Tnf Α ◽  
Mitogen Activated Protein

The prevalence of Candida infection induced by non-albicans Candida (NAC) species is increasing. However, as a common NAC species, C. tropicalis has received much less study in terms of host immunity than C. albicans has. In this study, we evaluated the pro-inflammatory cytokine responses evoked by C. tropicalis and determined whether dectin-1 and downstream NF-κB and mitogen-activated protein kinases (MAPKs) signaling pathways played roles in inflammation in human peripheral blood mononuclear cells (PBMCs) and THP-1 macrophage-like cells. Exposure of PBMCs and THP-1 macrophage-like cells to C. tropicalis led to the enhanced gene expression and secretion of TNF-α and IL-6 in a time- and dose-dependent manner. THP-1 macrophage-like cells being challenged by C. tropicalis resulted in the activation of the NF-κB, p38, and ERK1/2 MAPK signaling pathways. We also found that the expression of dectin-1 was increased with C. tropicalis treatment. These data reveal that dectin-1 may play a role in sensing the inflammation response induced by C. tropicalis and that NF-κB and MAPK are involved in the downstream signaling pathways in macrophages.

EPIDEMIOLOGICAL AND ETIOLOGICAL PROFILE OF IUFD: A PROSPECTIVE STUDY AT TERTIARY CARE CENTRE

2021 ◽  
pp. 31-34
Author(s):  
Deepali Jain ◽  
Uma Jain ◽  
Japhia David
Keyword(s):  
Gestational Age ◽  
Fetal Death ◽  
Health Centre ◽  
Tertiary Care ◽  
Mode Of Delivery ◽  
National Level ◽  
Health Indicators ◽  
Fetal Mortality ◽  
Hypertensive Disorder ◽  
Tertiary Care Centre

Introduction:- IUFD occurrence without warning in a previously normal pregnancy is really a challenge to obstetrician and distressing situation for parents. It becomes crucial to identify specic probable cause of fetal death, to prevent the re-occurance and get the corrective measures. Prenatal mortality is still of one of the top most health indicators in measuring the quality and impact of health services in developing countries Still birth is a useful index to measure the values of antenatal and intranatal care. To decrease the fetal mortality rate, evaluation, documentation and audit of the etiology and the associated risk factors for stillbirth is required. Material and method :- The present study aims at studying the various causes related to IUFD. Prospective observational study conducted on 112 patients at Department of Obstetrics and Gynaecology, Kamla Raja Hospital, G.R. Medical College and J.A. Group of Hospitals, Gwalior (M.P.) for 18 months. All those cases who were diagnosed as intrauterine dead fetus at the time of admission with gestational age >24 weeks pregnancy were included in the study. All those investigation available at the centre of mother and father were noted and details were taken. Epidemiological evaluation of causes of fetal death was done. Record of the method of induction and mode of delivery taken. RESULTS :-Total 112 cases found during the study period were included . We found maximum cases unbooked - 71.43%, which were mainly emergency admissions. Majority of the IUFD cases- 77.67% were found to lie in the age group of 20-30 yrs, most of them were primigravida 62.5%., maximum cases of IUFD were of the gestational age 31-35 weeks- 47.32%. Hypertensive disorder of pregnancy- 23.3 % cases were found to be the major associated cause followed by Antepartum Haemorrhage 11.5%, Severe anaemia 15.1%, diabetes- 14.2% jaundice - 9.8%. congenital anomaly- 9.8%. Oligohydromnios- 8.9% and IUGR were also found to be associated with IUFD, forming an indirect reason. 39.29% cases were unexplained. 86.6% cases delivered vaginally. 10.7% cases had to undergo LSCS and only 2.68% cases underwent laparotomy for rupture uterus. 11.61% cases were of macerated IUFD baby indicating long term neglected IUFD. 39.78% and 38.39% IUFD were of 2.0-2.5 kg and 1.5-2.0 kg. This show strong corelation with LBW and IUGR. CONCLUSION:- Unexplained cases, hypertensive disorder, anemia and diabetes were the major causes for IUFD. In spite of advances in diagnostic and therapeutic modalities a major cause of fetal death remain unexplained because of poverty, illiteracy, unawareness and inaccessibility of a health centre. Undoubtedly, continued surveillance of stillbirth rates is wanted for both high- and low-risk pregnancies at a state and national level.

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