Characterization of Promoter Activities of Four Different Japanese Flounder Promoters in Transgenic Zebrafish An important consideration in transgenic research is the choice of promoter for regulating the expression of a foreign gene . In this study several tissue-specific and inducible promoters derived from Japanese flounder Paralichthys olivaceus were identified , and their promoter activity was examined in transgenic zebrafish . The 5 ′ flanking regions of the Japanese flounder complement component C3 , gelatinase B , keratin , and tumor necrosis factor -LRB- TNF -RRB- genes were linked to green fluorescence protein -LRB- GFP -RRB- as a reporter gene . The promoter regulatory constructs were introduced into fertilized zebrafish eggs . As a result we obtained several stable transgenic zebrafish that displayed green fluorescence in different tissues . Complement component C3 promoter regulated GFP expression in liver , and gelatinase B promoter regulated it in the pectoral fin and gills . Keratin promoter regulated GFP expression in skin and liver . TNF gene promoter regulated GFP expression in the pharynx and heart . TNF promoter had lipoplysaccharide-inducible activity , such that when transgenic embryos were immersed lipopolysaccharide , GFP expression increased in the epithelial tissues . These 4 promoters regulated the expression of GFP in different patterns in transgenic zebrafish . Introduction Transgenic technology is a powerful tool not only for analyzing molecular biological functions but also for obtaining commercially important traits for aquaculture . In the last decade fish transgenesis has become common and has progressed considerably -LRB- Chen et al. , 1996 ; Hackett and Alvarez , 2000 -RRB- . Various transgenic fish that possess commercially important traits , such as growth enhancement -LRB- Zhang et al. , 1990 -RRB- or disease resistance -LRB- Sarmasik et al. , 2002 -RRB- , have been generated . One of the most critical factors in transgenic research is the regulation of foreign gene expression . Early fish transgenic research was conducted using housekeeping gene promoters such as β-actin -LRB- Liu et al. , 1990 ; Higashijima et al. , 1997 ; Hwang et al. , 2003 ; Noh et al. , 2003 -RRB- and elongation factor -LRB- EF -RRB- -LRB- Gao et al. , 1997 ; Kinoshita et al. , 2000 -RRB- . These promoters resulted in excess expression in various tissues . However , tissue-specific or inducible promoters are needed to regulate foreign genes in different situations . The activities of tissue-specific promoters were assessed in zebrafish using green fluorescence protein -LRB- GFP -RRB- as a reporter gene -LRB- Udvadia and Linney , 2003 -RRB- . This technique has provided a powerful tool for analyzing the regulation of gene expression in living fish . The pattern of expression of GFP in these transgenic zebrafish was the same as that of the gene from which the promoter was derived . However , promoters derived from most marine aquaculture species have not been described . To generate transgenic aquaculture fish , tissue-specific and stress-inducible promoters from these species need to be identified . Japanese flounder Paralichthys olivaceus is widely cultured and one of the most important food fish in East Asia . Because this industry is seriously affected by disease , the development of disease-resistant strains is a high priority . Previous studies by our laboratory have used expressed sequence tags -LRB- ESTs -RRB- -LRB- Aoki et al. , 1999 , 2000 ; Nam et al. , 2000 , 2003 -RRB- and molecular genetic analyses , especially of immune-related genes in Japanese flounder -LRB- Hirono et al. , 2003 -RRB- . In these reports we focused on cDNA clones that displayed tissue-specific expression or inducible expression , and 4 Japanese flounder genes were chosen for this study : complement component C3 , gelatinase B , keratin , and tumor necrosis factor -LRB- TNF -RRB- genes . These genes were chosen because they were revealed to be expressed in specific tissues of Japanese flounder by EST analysis . We assumed that the promoter region of these genes would show tissue-specific or inducible activities . It is possible to generate an effective transgenic fish using tissue-specific or inducible promoters . Indeed , such promoters can regulate foreign gene expression faithfully . In contrast , use of a housekeeping gene promoter would result in nonspecific expression -LRB- i.e. , overexpression -RRB- of foreign genes that may be harmful to the host fish . In this study we developed several Japanese flounder promoters that showed tissue-specific or inducible gene expression with the aim of using these in Japanese flounder . Although we have succeeded in introducing a foreign gene into Japanese flounder fertilized eggs and shown transient expression in Japanese flounder embryos , it has been difficult to conduct promoter assays in vivo because the technology has not been sufficiently developed to produce transgenic Japanese flounder with the necessary efficiency . However , the transgenic zebrafish model system has the advantages of shorter generation time , better optical transparency , and easier treatment schemes when compared with Japanese flounder . In this study , promoter regions of the complement component C3 , gelatinase B , keratin and TNF genes were isolated and their promoter activities were characterized in transgenic zebrafish . Materials and Methods mRNA Expression in Japanese Flounder Tissues Total RNA was extracted from spleen , fin , liver , head kidney , post kidney , skin , blood , heart , intestine , ovary , gill , leukocyte , and peripheral blood leukocytes -LRB- PBLs -RRB- stimulated with lipopolysaccharide -LRB- LPS -RRB- using TRIzol -LRB- Invitrogen -RRB- . The purified total RNA -LRB- 10 μg -RRB- was reverse transcribed into cDNA using an avian myeloblastosis virus -LRB- AMV -RRB- transcriptase First-strand cDNA synthesis kit -LRB- Amersham Bioscience -RRB- . The reverse-transcribed sample -LRB- 1 μl -RRB- was used in 50 μl of PCR mixture . The PCR primers for Japanese flounder complement component C3 mRNA detection were -LRB- sense -RRB- 5 ′ - GCTGGAGAAAG TCGTCTTGG-3 ′ and -LRB- anti -RRB- 5 ′ - GGATACCTCTCAACTCTG CC-3 ′ , gelatinase B mRNA detection , -LRB- sense -RRB- 5 ′ - GCA GGAGCCACCAGTCAAAA-3 ′ and -LRB- anti -RRB- 5 ′ - GGTCCAGTG TTCATCATCGT-3 ′ , keratin mRNA detection , -LRB- sense -RRB- 5 ′ - ACTCCGTCGCACAATGCAGA-3 ′ and -LRB- anti -RRB- 5 ′ - CTGCA ATTTCCATCTCCAGC-3 ′ , and TNF mRNA detection , -LRB- sense -RRB- 5 ′ - CCCTATGAACTGTAACAGTTTG-3 ′ and -LRB- anti -RRB- 5 ′ - GTCAGGTACTTAACCCTCAT-3 ′ . The ß-actin primer set for an internal control was -LRB- sense -RRB- 5 ′ - TTTCCCT CCATTGTTGGTCG-3 ′ and -LRB- anti -RRB- 5 ′ - GCGACTCTCAGCTC GTTGTA-3 ′ . The PCR was performed with an initial denaturation step of 2 minutes at 95 °C and then 20 cycles were run as follows : 30 seconds of denaturation at 95 °C , 30 seconds of annealing at 55 °C , and 1 minute of extension at 72 °C . The reaction products were electrophoresed in a 2.0 % agarose gel . Identification of 5 ′ Flanking Region Sequences The 5 ′ flanking regions of 4 genes were isolated from a Japanese flounder genomic BAC library -LRB- Katagiri et al. , 2000 -RRB- using cDNA clones of complement component C3 -LRB- AB021653 -RRB- , gelatinase B -LRB- AU091035 -RRB- , keratin -LRB- AB079729 -RRB- , and TNF -LRB- AB040448 -RRB- , as probes for gene screening . To determine the transcription start site , the primer extention method was performed according to a modified version of that in Hikima et al. -LRB- 2001 -RRB- . A 20mer synthetic oligonucleotide corresponding to the complementary sequence of the first exon was labeled with fluorochrome . The fluorochrome-labeled primer was hybridized to 10 μg of kidney total RNA -LRB- extracted using Trizol , Invitrogen -RRB- and then extended using an AMV reverse transcriptase first-strand cDNA synthesis kit -LRB- Amersham Bioscience -RRB- . Subcloned plasmid DNA , containing the first exon of each gene , was adopted as a template for the sequencing using the same fluorochrome-labeled primer . The sequence products were analyzed with primer-extended cDNA fragment by the cycle sequencing method . Construction of Promoter-EGFP Plasmid The reporter gene vector pEGFP-1 -LRB- Clontech -RRB- was used for the construct . Four different Japanese flounder promoters including 5 ′ untranslated region -LRB- UTR -RRB- were amplified by specific PCR primers and inserted into the multiple cloning site of pEGFP-1 . GFP reporter gene was the endogenous initiation codon directly replaced with that of GFP . To confirm the sequence and direction of insert , the recombinant plasmid was sequenced using a Thermo Sequenase II kit and automated DNA sequencer 373A with a primer designed for pEGFP-1 . Production of Transgenic Zebrafish Adult zebrafish -LRB- Danio rerio -RRB- and embryos were maintained at 28.5 °C on a 14-hour light and 10-hour dark cycle . The recombinant plasmid was propagated in Escherichia coli JM109 and purified using a GFX Micro Plasmid prep kit -LRB- Amersham Biosciences -RRB- . Purified plasmid DNA was adjusted to 50 ng/μl in distilled water and microinjected into one-celle-stage zebrafish embryos . Initially 400 to 500 embryos were injected with plasmid DNA in each promoter-GFP construct . Living embryos were examined under an SZX12 fluorescence microscope -LRB- Olympus -RRB- , and GFP-positive zebrafish embryos were selected . After maturation the GFP-positive fish were mated with wild types to select fish for germline transmission . GFP expression in F1 embryos was also examined under the fluorescence microscope in each developmental stage . LPS Treatment of TNF-GFP Transgenic Zebrafish Embryo F2 generations of transgenic zebrafish injected with TNF-GFP at 30 hours postfertilization -LRB- hpf -RRB- were stimulated with LPS -LRB- Sigma -RRB- at 140 μg/ml for 30 minutes and then washed in sterilized water . GFP expression in F2 embryos was examined under the fluorescence microscope at 48 hpf . Detection of GFP Gene Expression in Adult Transgenic Zebrafish by RT-PCR Total RNA extraction and PCR was performed as described above . Total RNA was extracted from fin , skin , liver , kidney , muscle , and brain of adult transgenic zebrafish . The following PCR primers were designed for the detection of EGFP gene : GFP-F , 5 ′ - GGTCG AGCTGGACGGCGACG-3 ′ , and GFP-R , 5 ′ - ACGAACTCC AGCAGGACCAT-3 ′ . The zebrafish ß-actin primer set for internal control was zactin-F , 5 ′ - TTTCCCTCCATT GTTGGTCG-3 ′ , and zactin-R , 5 ′ - GCGACTCTCAGCTCG TTGTA-3 ′ . Results and Discussion The expression of complement component C3 , gelatinase B , keratin , TNF and β-actin genes in Japanese flounder was detected by reverse transcriptase polymerase chain reaction -LRB- RT-PCR -RRB- . The complement component C3 gene was expressed only in the liver . The gelatinase B gene was expressed in the kidney , blood , and leukocytes . The keratin gene was expressed in various tissues . The TNF gene was expressed only in PBLs when stimulated with LPS . The β-actin gene used as an internal control was expressed in all tissues -LRB- Figure 1 -RRB- . Thus the expression patterns of these genes were different in different Japanese flounder tissues . We assumed that the tissue-specific and inducible expression of these genes was regulated by their promoter region.Fig . 1 . Expression of Japanese flounder tissue-specific genes in different tissues . Messenger RNA expression of complement component C3 , gelatinase B , keratin , and TNF genes in spleen , fin , liver , head kidney , post kidney , skin , blood , heart , intestine , ovary , gills , leukocyte , and PBLs stimulated with LPS from Japanese flounder were detected by RT-PCR . The 5 ′ flanking regions of the genes for complement component C3 -LRB- 1381 bp -RRB- , gelatinase B -LRB- 1420 bp -RRB- , keratin -LRB- 1288 bp -RRB- , and TNF -LRB- 2351 bp -RRB- were isolated , and the respective transcriptional initiation sites were determined -LRB- Figure 2 -RRB- . There were some predicted transcriptional factor binding sites , such as TATA box , CAAT box or NF-κB binding site , in the 5 ′ flanking region . These sites were highly homologous with mammalian transcriptional factor binding sites . It is not certain that these predicted transcriptional factor binding sites can be applied to Japanese flounder promoters as there are few reports on fish transcriptional factor binding protein . It should be interesting to determine if these transcriptional factor binding sites are common to mammal and fish . These promoter regions were cloned into pEGFP-1 plasmid vector . These promoter regulatory constructs were designated C3-GFP , gelatinase-GFP , keratin-GFP , and TNF-GFP , respectively.Fig . 2 . The 5 ′ flanking region sequence of the Japanese flounder gene : complement component C3 -LRB- A -RRB- ; gelatinase B -LRB- B -RRB- ; keratin -LRB- C -RRB- ; and TNF gene -LRB- D -RRB- . We isolated 1381 bp of the 5 ′ flanking regions from transcription initiation codon for complement component C3 ; 1420 bp for gelatinase B ; 1288 bp for keratin ; and 2351 bp for TNF . The first exon is indicated in capital letters . The coding region and deduced amino acids are indicated in boldface capital letters . The transcription initiation site is shown by an asterisk . The predictive transcriptional factor binding site is underlined . We obtained F1 transgenic individuals using each promoter regulatory constructs . An F2 strain was established with the C3-GFP , gelatinase-GFP , and keratin-GFP construcst , and two F2 strains from two different founders were established with the TNF-GFP construct . Similar GFP expression patterns were shown in F1 individuals and their F2 strains . GFP expression controlled by the complement component C3 promoter was observed in the yolk sac from the gastrula stage , in F2 transgenic zebrafish strains . In 10-day embryos strong GFP expression was observed only in the liver -LRB- Figure 3 -RRB- . GFP expression could not be observed in adults . The RT-PCR analysis showed that complement component C3 promoter also induced GFP expression in the adult liver -LRB- see Figure 7 -RRB- . Fish complement component C3 gene has the same function as the mammalian gene , and is expressed mainly in the liver -LRB- Abelseth et al. , 2003 -RRB- . Japanese flounder complement component C3 was also expressed mainly in the liver -LRB- Figure 1 -RRB- . This was similar to the promoter activity observed in transgenic zebrafish . This suggests that Japanese flounder complement component C3 promoter could also induce expression of genes in the same tissues in zebrafish.Fig . 3 . GFP expression in C3-GFP transgenic zebrafish embryos . The larval embryos at 24 hpf -LRB- A -RRB- and liver of the 10-day embryos -LRB- B -RRB- of F2 transgenic strain . Arrowheads indicate bladder and eye . GFP expression regulated by the gelatinase B promoter was observed after the one-cell stage , and was expressed strongly in the whole body until 48 hpf . However , GFP expression in the whole body decreased in the course of development . In 5-day embryos , strong GFP expression was detected only in the pectoral fins and gills -LRB- Figure 4 -RRB- . In adult transgenic fish gelatinase B promoter regulated GFP expression in the fin -LRB- see Figure 7 -RRB- . This result agrees with the GFP expression at embryonic stage . The GFP expression under the control of the Japanese flounder gelatinase B gene promoter in the transgenic zebrafish was not identical with the expression of the gelatinase B gene in Japanese flounder , in which it was expressed mainly in hematopoietic tissues -LRB- Figure 1 -RRB- . This promoter may lack a region essential for tissue-specific expression.Fig . 4 . GFP expression of gelatinase B-GFP transgenic zebrafish . GFP expression at one-cell stage -LRB- A -RRB- , 7 hpf -LRB- B -RRB- , 12 hpf -LRB- C -RRB- , 48 hpf -LRB- D -RRB- , and 5-day embryo , lateral view -LRB- E -RRB- and dorsal view -LRB- F -RRB- . The keratin promoter regulated strong GFP expression from the embryo stage to the adult stage . In the embryo strong GFP expression was observed in the epithelial tissues and liver . In adult fish GFP expression was detected in skin , gills , fins , and liver -LRB- Figure 5 -RRB- . This expression pattern was similar to that of the Japanese flounder keratin gene -LRB- Figure 1 -RRB- . The zebrafish keratin 8 promoter was found to induce expression only in the skin -LRB- Gong et al. , 2002 -RRB- . These results indicate that the promoter of the Japanese flounder keratin gene induces gene expression in the same tissues in zebrafish as in Japanese flounder . However , the sequences of the keratin promoter region of zebrafish and Japanese flounder are not the same -LRB- data not shown -RRB- . This may be because some transcription factors that enhance skin-specific expression in zebrafish can bind and enhance the promoter activity of keratin promoter derived from Japanese flounder in transgenic zebrafish embryo.Fig . 5 . GFP expression in keratin-GFP F2 transgenic zebrafish under the fluorescence microscope . A : The 4-day embryo . B : Adult fish . C : Adult fish with operculum removed and abdominal muscle surgically opened . Arrowheads indicate gill and liver . The TNF promoter regulated GFP expression only in the heart and pharynx in 5-day embryos . GFP expression was strongly induced in the epithelial tissues in 2-day transgenic embryos after LPS treatment -LRB- Figure 6 -RRB- . GFP expression was not detected in adult transgnic zebrafish by RT-PCR . This result suggested that TNF promoter controlled GFP expression in transgenic zebrafish under normal conditions -LRB- Figure 7 -RRB- . The Japanese flounder TNF promoter has inducible activity in zebrafish similar to that of Japanese flounder TNF gene expression in LPS-stimulated PBLs -LRB- Hirono et al. , 2000 -RRB- . These results suggest that the Japanese flounder TNF promoter used in this study is sufficient to regulate the expression of a downstream gene.Fig . 6 . GFP expression in TNF-GFP transgenic zebrafish under the fluorescence microscope . A : The 5-day embryo of wild type . B : F2 transgenic strain , 5-day embryo . Arrowheads indicate heart and pharynx . C : Nontreated 3-day transgenic zebrafish embryo . D : LPS-treated 3-day transgenic zebrafish embryo.Fig . 7 . Detection of mRNA expression of GFP gene in fin , skin , liver , kidney , muscle , and brain from adult transgenic zebrafish by RT-PCR . GFP expression regulated by TNF promoter was not detected . N.C. indicates negative control . In this study we showed that heterologous promoters derived from Japanese flounder worked in transgenic zebrafish . However , the expression patterns different from endogenous Japanese flounder expression patterns . Notably , the keratin and TNF promoters seemed to work faithfully in zebrafish embryos , but the gelatinase B promoter result differed from the results predicted from Japanese flounder . This may have been due to the short 5 ′ flanking region used in this study . Furthermore , we only observed the GFP expression pattern in a single transgenic line . Whether this GFP expression pattern is representative of gelatinase B promoter activity needs to confirmed in future studies by establishing multiple transgenic lines . Similarly , the fate of these promoters in Japanese flounder needs to be determined by production of transgenic lines of Japanese flounder . The Japanese flounder promoters developed in this study can be adapted for transgenic fish in a variety of situations . Keratin promoter induced expression in epithelial tissues , where it acts as a first line of defense against bacterial infection . It is possible to generate disease-resistant transgenic fish expressing an antibacterial or antiviral peptide only in epithelial tissues . Moreover , using the Japanese flounder TNF promoter , it is possible to generate transgenic fish expressing an antibacterial or antiviral peptide only in cases of infection with pathogens . Thus these promoters should be useful for production of disease-resistant transgenic fish . The overexpression of a foreign gene , especially the gene for an antimicrobial peptide , may suppress growth or maturity of the host fish . In addition , these transgenic fish are safe for human consumption , as the foreign gene is not expressed in the muscle . The Japanese flounder TNF gene promoter can also be used to monitor bacterial infection in live fish using GFP as an indicator . Furthermore , these transgenic zebrafish were suitable for developmental analysis of specific tissues or organs . It is possible to observe development of liver , gills , and skin in living embryos using GFP expression . We also developed a method for introducing a gene into Japanese flounder fertilized eggs by particle gun bombardment -LRB- Yazawa et al. , 2005 -RRB- . The development of tissue-specific , inducible promoters in this study will support the establishment of transgenic technology for Japanese flounder and should contribute to a better understanding of the biology and culture of this fish species .

O O O O O O O B I O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O B I O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O 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O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O B I O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O B I O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O B I O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O B I O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O B I O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O B I O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O

tissue-specific promoter
inducible promoter
green fluorescence protein (gfp)


Do We Practice What We Preach ? A Review of Actual Clinical Practice with Regards to Preconception Care Guidelines Objectives : To review what past studies have found with regard to existing clinical practices and approaches to providing preconception care . Methods : A literature review between 1966 and September 2005 was performed using Medline . Key words included preconception care , preconception counseling , preconception surveys , practice patterns , pregnancy outcomes , prepregnancy planning , and prepregnancy surveys . Results : There are no current national recommendations that fully address preconception care ; as a result , there is wide variability in what is provided clinically under the rubric of preconception care . Conclusions : In 2005 , the Centers for Disease Control and Prevention sponsored a national summit regarding preconception care and efforts are underway to develop a uniform set of national recommendations and guidelines for preconception care . Understanding how preconception care is presently incorporated and manifested in current medical practices should help in the development of these national guidelines . Knowing where , how , and why some specific preconception recommendations have been successfully adopted and translated into clinical practice , as well as barriers to implementation of other recommendations or guidelines , is vitally important in developing an overarching set of national guidelines . Ultimately , the success of these recommendations rests on their ability to influence and shape women 's health policy . There is a strong body of evidence to demonstrate that preconception care can modify behavioral , medical , and other health risk factors known to impact pregnancy outcomes . For example , preconception care efforts and interventions have been shown to improve folate status among women planning to conceive and to reduce the risk of fetal alcohol syndrome -LSB- 1 , 2 -RSB- . Controlling known medical problems prior to pregnancy not only helps to optimize the mother 's health , it may also improve neonatal and pediatric outcomes -LSB- 3 -RSB- . Preconception care efforts and interventions have been shown to lower the risk for both major and minor birth defects among the children of women with pre-existing diabetes -LSB- 4 -RSB- . Women with epilepsy and their offspring benefit from preconception care counseling that manages medications , optimizes seizure control and prescribes folic acid for neural tube defect -LRB- NTD -RRB- prevention -LSB- 5 , 6 -RSB- . While there is a burgeoning knowledge base on how to improve pregnancy outcomes , there are few studies examining the effects of this knowledge base on actual practice patterns . It is not well known to what extent health care providers are translating preconception care knowledge into practice for all women capable of becoming pregnant -LRB- whether planning pregnancy or not -RRB- . Material and methods A literature review between 1966 and September 2005 was performed using Medline to examine the impact of preconception care trials and recommendations on the clinical practice patterns of health care providers . Key words included preconception care , preconception counseling , preconception surveys , practice patterns , pregnancy outcomes , prepregnancy planning , and prepregnancy surveys . Relevant review articles regarding preconception care were also included . All studies had to be done in the United States . Studies that examined existing clinical practices and approaches directly to providing preconception care were eligible for inclusion . Studies that used indirect methods of measurement , e.g. , interviews with women as a means of assessing preconception care practices of providers , were not included . A total of 11 studies were located and included analyses of practice patterns of various health care providers and specialties -LRB- see Appendix -RRB- . Results Studies researching health care provider awareness , knowledge and practices regarding preconception care in the United States are infrequently performed , so it is difficult to fully assess health care provider approaches and practices related to preconception care . A small pilot study involving family practice nurse practitioners was done in 1987 to determine what preconception care issues were discussed with women of childbearing age during a well woman visit . Audiotapes of the visits were compared to an investigator-developed model for preconception counseling . Based on the results , the authors concluded that current obstetrical care had not expanded to include preconception counseling -LSB- 7 -RSB- . A study among family physicians conducted in 1991 using the Comprehensive Prevention Knowledge and Applications Survey Instrument found that only 37 % of providers reported counseling women of childbearing age about preconception behaviors > 75 % of the time -LSB- 8 -RSB- . When asked how often they felt ready to counsel women on preconceptional factors , about 70 % of providers said they were prepared at least three-fourths of the time . However , perceived preparedness did not equate to counseling success . Among providers who did counsel , only about one-third reported being successful at helping their patients change preconceptional behaviors at least 75 % of the time . A 1991 study conducted among family practice and internal medicine residents in an inner-city public hospital found that both groups of residents reported low levels of knowledge and management decision skills regarding preconception care when compared with standard recommendations , despite their favorable attitudes towards preconception care -LSB- 9 -RSB- . In this survey , close to 50 % of the residents did not mention family planning during counseling sessions with women of reproductive age and 74 % would not raise the issue of congenital defects in their diabetic patients seeking to become pregnant . While both family practice and internal medicine residents had favorable attitudes towards preconception care , the family practice residents scored higher in positive attitude about preconception care . There was no difference between the groups in terms of management skills , and there was no sustained difference between groups in the area of knowledge . Previous rotation through a high-risk perinatal clinic increased scores in areas of management and knowledge compared to family practice or internal medicine residents who had not rotated through such a clinic , but these differences were not significant -LSB- 9 -RSB- . In an effort to assess the practices of genetic counseling and screening for consanguineous couples , their pregnancies , and their children , 1,582 surveys were mailed to board certified genetic counselors and medical geneticists in the United States in 1999 -LSB- 10 -RSB- . While the response rate was very poor -LRB- only 20 % -RRB- there was wide variability in suggested screening practices for consanguineous couples before conception , during pregnancy , after birth , and for children placed for adoption . Respondents seemed to generally agree to do screening based on ethnicity but there was no consistency regarding which genetic disorders to include in these screening efforts . A mailed survey of obstetrician-gynecologists in 2000 focused on issues around folate for the prevention of NTDs -LSB- 11 -RSB- . Almost 97 % of participants knew that when taken early enough , folic acid reduced the incidence of NTDs . While two-thirds of respondents said they routinely screened their pregnant patients for folate intake , only 53 % screened nonpregnant women of childbearing age . The authors of the study concluded that most obstetrician/gynecologists are aware of the link between folate intake and NTDs although the data showed that physicians who routinely screened for folate intake correctly answered more survey questions than those who did not . As part of a larger effort to improve the documentation and delivery of preconception care , Bernstein and colleagues evaluated the knowledge base and awareness of preconception care for women in their childbearing years seeking care in an inner city outpatient gynecology clinic in 2000 -LSB- 12 -RSB- . Providers in the clinic included physicians and nurse practitioners . A pre-intervention chart review found that many of the providers were not addressing family planning services , domestic violence , nutrition and medical risk factors , medication use , appropriate counseling and use of referral services during gynecologic visits . The authors concluded that the providers did not take the opportunity to discuss preconception care during routine gynecologic visits . A series of studies looking at provider knowledge and practice regarding preconception and prenatal screening for cystic fibrosis -LRB- CF -RRB- was conducted during 2001 -- 2004 using the Collaborative Ambulatory Research Network -LRB- CARN -RRB- -LSB- 13 -RSB- . Results showed that almost one-half of the responders did not ask nonpregnant women of childbearing age about their family history of CF , nor did they provide information on CF screening . Close to 90 % of respondents did offer CF screening or inquire about a family history of CF among pregnant women . Of those Ob/Gyns who did selectively screen for CF among their pregnant patients , about 25 % utilized all of the selection criteria noted in the American College of Obstetricians and Gynecologists -LRB- ACOG -RRB- recommendations . In 2002 and 2003 the March of Dimes examined folic acid knowledge and practice patterns of health care providers in obstetric/gynecology and family/general practice settings -LSB- 14 -RSB- . Survey results found that , while knowledge about the need for supplementation and timing of folic acid was high , increased knowledge about unintended pregnancy rates and correct doses of folic acid for prevention of occurrence and recurrence of NTDs is needed . A little more than half of all providers knew the correct dose of folic acid -LRB- 400 mcg daily -RRB- for the prevention of NTDs . This percentage dropped dramatically when providers were asked the correct dose of folic acid for a woman with a history of a previous NTD-affected pregnancy . Almost two-thirds of providers did not know the folic acid dose for recurrence prevention -LRB- 4 mg daily -RRB- . In the surveys , the vast majority of providers reported always recommending folic acid supplementation for women who expressed interest in becoming pregnant , approximately 60 % of respondents who provide prenatal care reported seeing less than one fifth of their prenatal patients for a preconception care visit -LSB- 14 -RSB- . At annual gynecologic or well-woman examinations as well as other types of patient visits , less than 60 % of respondents always or usually addressed supplementation . Lack of knowledge -LRB- 39 % -RRB- and lack of time -LRB- 30 % -RRB- during a busy exam schedule were the most cited reasons providers gave for not always recommending folic acid . In 2004 a survey was sent to Florida health care providers to establish their baseline knowledge and practice behavior regarding folic acid and NTDs -LSB- 15 -RSB- . At baseline , 97 % of providers reported awareness of the protective nature of folic acid during preconception and early in the first trimester ; however , less than half of providers reported that they discuss folic acid consumption with all women of child-bearing age . After a statewide educational program , the same providers were surveyed again to see if there had been any change in knowledge base or practice patterns . The survey done after the educational outreach efforts did demonstrate an increase in awareness and an increase in the percentage of providers who recommended peri-conceptional use of folic acid to prevent NTDs . The authors note , however , that despite these modest gains , the need for continued education and modification of provider practice patterns remains . A recent survey by ACOG was done to assess the opinions and practices of obstetrician-gynecologists regarding preconception care , and their perception of patients ' receptiveness to preconception services -LSB- 16 -RSB- . The vast majority of physicians -LRB- 97.3 % -RRB- stated that they provide preconception care for their patients , although obstetrician-gynecologists were more likely to do so than providers who only practiced gynecology . The majority of physicians -LRB- 87 % -RRB- agreed with the definition of preconception care as `` Specialized pre-pregnancy care that focuses on issues not typically addressed during a routine exam which are specific to ensuring an optimal pregnancy outcome . '' Most of the respondents indicated that women are more likely to present for preconception care to ensure a healthy pregnancy than because of an elevated risk for a birth defect or developmental disorder . The majority of physicians agreed that preconception care is an important issue and that it has a positive effect on pregnancy outcomes , though only 21 % agreed that it was a high priority in their workload . Half of the physicians said there was not enough time to provide preconception care to all women with reproductive potential , nor were there reimbursement incentives to do so . Discussion Preconception care - care that is initiated before pregnancy - is advocated to help women reduce their risk for adverse pregnancy outcomes and make informed decisions regarding their readiness for and timing of pregnancy -LSB- 17 -RSB- . Appropriate preconception care improves pregnancy outcomes and has several components . These include , but are not limited to : the systematic identification of preconceptional risks through an assessment of the woman 's reproductive , family , and medical history ; the family and medical history of the father ; the woman 's nutritional status , social concerns , and any drug or substance exposures she or the father may have -LRB- had -RRB- ; discussions regarding possible effects of any existing medical problems and potential interventions ; screening for infectious diseases with treatment and immunization where indicated ; discussions about environmental exposures , both occupational and household ; a review of the circumstances of the woman 's life and behavioral patterns ; counseling and discussion about birth spacing including real and perceived barriers to achieving her desires ; and inquiry and education regarding contraceptive use . Traditionally , preconception care endeavors have focused on women who have a chronic medical condition , a history of a poor outcome in a previous pregnancy , or who are planning to become pregnant in the near future . For women with chronic medical conditions , the effect -LRB- s -RRB- of their illness -LRB- es -RRB- range from minimal to limited activity to hospitalization . Drawing on information for the 1996 National Health Interview Survey -LRB- NHIS -RRB- , 9.9 % of women ages 18 -- 44 years had some limitations placed on their activity levels due to chronic disease -LSB- 18 -RSB- . There is clear evidence that the initiation of preconception counseling and care for women with some chronic health conditions , e.g. , diabetes , will positively impact pregnancy outcomes -LSB- 19 -RSB- . For women with a history of a poor pregnancy outcome in the past , pre - or interconceptional intervention strategies have been demonstrated to be effective -LSB- 20 -RSB- . Limiting preconception care endeavors to women actively planning pregnancy , however , reaches a limited audience as almost 50 % of pregnancies in the U.S. are unintended -LSB- 21 -RSB- . Comprehensive preconception care , however , encompasses much more than just these risk categories and is inclusive of all women with the potential to become pregnant . Women of childbearing age visit their physician an average of about three times per year ; these visits represent opportunities to deliver preconception care and messages related to preconception care -LSB- 22 -RSB- . In reviewing the literature related to the clinical practice of preconception care , it is clear that most of these opportunities are either missed or foregone . In an article focusing on preconceptional health promotion , Moos proposes 5 categorical reasons for why providers are inconsistent in applying proven prevention strategies for poor pregnancy outcomes : lack of knowledge regarding the incidence of unintended pregnancy , inadequate provider education , lack of confidence that preconceptional health counseling is valuable , a belief that women will ` know ' to seek the care appropriate to their needs , and concerns over lack of reimbursement coverage for preconceptional visits -LSB- 23 -RSB- . Changing behavior patterns is no small feat , but understanding the ` hows ' and ` whys ' of change -LRB- s -RRB- in provider practice patterns is becoming better understood . For example , in diffusion theory , diffusion is the process through which an innovation is adopted for use or application by a community -LSB- 24 -RSB- . One proposed method for facilitating diffusion of innovation utilizes an expert opinion leader process whereby a designated -LRB- or identified -RRB- local physician leader communicates information about new innovation -LRB- s -RRB- or knowledge to colleagues and then follows up with them about their personal experiences with the information -LSB- 25 -RSB- . This approach has demonstrated effectiveness for eliciting changes in practice patterns in certain situations and settings , but it is not uniformly effective in all instances -LSB- 26 -- 29 -RSB- . In his assessment of how research findings get translated into `` best practices '' , Green postulates that there are three areas representing barriers to the adoption of best practice : 1 -RRB- accessibility gap , i.e. , practitioners do not have the same resources available as the researchers ; 2 -RRB- credibility gap , e.g. , a comparison of differences in practice settings or populations that might ` explain ' why the research is not applicable to the general practitioner ; 3 -RRB- expectations gap , e.g. , the practitioner views the research findings as unnecessary goals to set for their own practices -LSB- 30 -RSB- . These barriers are not insurmountable , and there is evidence that different approaches to changing provider behavior patterns are effective -LSB- 26 , 27 -RSB- . In an article by Cullum , several model programs are reviewed that have demonstrated changes in the practices of health care providers related to preconception care -LSB- 31 -RSB- . Studies evaluating effective preconception care interventions and strategies are numerous , and continue to grow . There is also an increasing amount of information about how patients assimilate and act upon recommendations regarding preconception care . There is little data , however , that analyzes the impact and integration of preconception care innovations on daily clinical practice -LRB- s -RRB- . One limitation of this literature review is that articles with secondary goals of evaluating actual clinical practices may have been overlooked . Efforts were made to include all relevant search terms but it is possible that articles written before 1985 may have been inadvertently excluded if different keywords were used at that time . Nonetheless , there is a large need for further research into the contrast between the science of preconception care and the reality of actual clinical practice . Conclusion Preconception care seeks to promote the health of women of childbearing age prior to conception and to improve pregnancy-related outcome . Various authors propose the integration of preconception care into routine wellness care for all women of reproductive potential -LSB- 23 , 32 -- 34 -RSB- . The question is how do we raise the level of importance and prioritization of preconception care during individual encounters as well as on a national health policy level ? Proving the efficacy of a practice does not guarantee an actual change in practice and simply prompting providers to incorporate preconception care will not suffice . Creating the expectation that preconception care is an ongoing process during a woman 's reproductive life span will require a myriad of efforts concurrently directed at providers , patients , payors , and policy makers . In 2005 , the Centers for Disease Control and Prevention sponsored a national summit regarding preconception care with a broad cross-section of stakeholders . Efforts are currently underway to develop a uniform set of national recommendations and guidelines for preconception care . Understanding how preconception care is presently incorporated and manifested in current medical practices should help in the development of these national guidelines . Knowing where , how , and why some specific preconception recommendations have been successfully adopted and translated into clinical practice , as well as barriers to implementation of other recommendations or guidelines , is vitally important in developing an overarching set of national guidelines . Ultimately , the success of these recommendations rests on their ability to influence and shape women 's health policy .

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O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O B I O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O B I O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O B I O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O

preconception care
preconception counseling
preconception surveys
practice patterns
pregnancy outcomes
prepregnancy planning
prepregnancy surveys


A

Perspective

of

Preconception

Health

Activities

in

the

United

States

Objectives

Information

regarding

the

type

and

scope

of

preconception

care

programs

in

the

United

States

is

scant

We

evaluated

State

Title

V

measurement

and

indicator

data

and

abstracts

presented

at

the

National

Summit

on

Preconception

Care

-LRB-

June

-RRB-

in

order

to

identify

existing

programs

and

innovative

strategies

for

preconception

health

promotion

Introduction

The

June

National

Summit

on

Preconception

Care

sponsored

by

the

Centers

for

Disease

Control

and

Prevention

-LRB-

CDC

-RRB-

and

the

March

of

Dimes

assembled

an

array

of

health

care

providers

public

health

practitioners

and

researchers

in

an

effort

to

promote

the

exchange

of

information

and

ideas

related

to

preconception

care

at

the

local

state

and

national

levels

A

key

issue

emerging

from

conference

discussions

was

the

perceived

lack

of

information

pertaining

to

the

nature

and

scope

of

preconception

health

services

currently

being

provided

in

the

United

States

whether

explicitly

defined

or

falling

under

another

umbrella

of

services

Another

issue

was

the

recognition

that

a

compilation

of

local

state

and

national

resources

would

provide

important

information

related

to

the

ability

of

current

public

health

systems

to

address

preconception

care

needs

as

well

as

allow

for

the

description

of

innovative

models

for

the

delivery

of

such

services

Attended

by

more

than

registered

participants

representing

a

myriad

of

agencies

and

organizations

the

summit

generated

significant

response

within

the

public

health

and

clinical

communities

and

reflects

a

perspective

that

can

not

be

readily

gleaned

from

literature

reviews

or

the

inspection

of

existing

programmatic

guidelines

that

is

the

topic

of

preconception

health

has

garnered

substantial

interest

and

support

and

has

already

been

incorporated

into

numerous

existing

programs

policies

and

strategies

in

the

United

States

Unique

to

the

summit

was

an

opportunity

to

learn

about

the

development

and

administration

of

preconception

care

programs

within

clinical

and

population-based

settings

as

Medline

PubMed

and

other

Internet

searches

have

revealed

very

little

information

regarding

the

development

and

implementation

of

preconception

care

programs

within

a

local

context

However

as

evidenced

by

the

numerous

programmatic

components

featured

in

the

conference

abstracts

such

programs

are

being

introduced

in

many

different

formats

among

various

private

and

public

organizations

and

across

the

entire

nation

Although

little

is

now

known

at

this

writing

about

the

scope

and

extent

of

U.S.

programs

and

projects

to

promote

preconception

health

this

article

uses

readily

available

sources

-LRB-

in

the

published

professional

literature

and

the

gray

literature

of

government

and

organization

reports

-RRB-

to

provide

a

snapshot

of

related

activities

in

the

United

States

Thus

we

are

able

to

report

the

findings

of

a

scan

of

State

Title

V

Performance

Measures

and

Priority

Needs

pertaining

to

preconception

care

and

a

detailed

summary

of

the

abstracts

of

the

papers

presented

at

the

Summit.Fig

Title

V

priority

needs

focused

on

preconception

health

and

health

care

U.S.

Methods

The

Maternal

and

Child

Health

Bureau

website

-LRB-

-RRB-

was

used

to

ascertain

the

proportion

of

states

including

preconception

health

indicators

in

State

Performance

Measures

and

Priority

Needs

as

reported

in

the

State

Title

V

Maternal

and

Child

Health

Service

-LRB-

MCH

-RRB-

Block

Grant

FY

Annual

Report

and

FY

Application

Form

The

web-based

Title

V

Information

System

-LRB-

measureindicatemenu.asp

-RRB-

was

used

to

search

State

Title

V

Performance

Measures

and

Priority

Needs

for

indicators

related

to

preconception

health

Initial

search

parameters

included

all

keywords

and

all

populations

and

were

further

refined

by

selecting

for

birth

outcomes

reproductive

health

and

women

Those

indicators

for

which

infants

newborns

children

men

or

service

providers

represented

the

sole

target

population

were

excluded

The

remaining

measures

were

evaluated

based

on

their

relevancy

to

preconception

health

Indicators

using

the

term

preconception

or

preconceptual

and

those

that

did

not

use

such

terminology

but

adequately

captured

the

concept

were

considered

to

fall

within

the

domain

of

preconception

health

and

health

care

States

identifying

preconception

health

Priority

Needs

were

depicted

on

a

national

map

States

reporting

relevant

Performance

Measures

were

identified

and

selected

measures

were

described

in

tabular

format

Finally

a

comprehensive

list

of

State

Title

V

Performance

Measures

and

Priority

Needs

related

to

preconception

health

that

reflected

the

tone

and

language

of

multiple

states

was

developed

All

abstracts

submitted

and

accepted

for

presentation

at

the

National

Summit

on

Preconception

Care

-LRB-

June

-RRB-

were

pooled

and

subjectively

categorized

into

five

broad

topic

areas

research

pertaining

to

preconception

risk

assessment

and

outcome

evaluation

preconception

care

programs

and

activities

tools

intended

for

provider

or

patient

preconception

health

education

clinical

practice

strategies

and

public

policy

related

to

preconception

care

Results

State

Title

V

Performance

Measures

and

Priority

Needs

The

federal

MCH

Block

Grant

guidance

requires

states

to

report

annually

on

National

Core

Performance

Measures

and

to

assess

needs

and

set

priorities

every

years

In

addition

each

state

must

develop

to

additional

Performance

Measures

relevant

to

its

own

priority

needs

and

programs

Priority

Needs

reflect

a

state

's

focus

for

programmatic

efforts

throughout

the

next

five

years

and

can

be

adjusted

during

interim

years

in

response

to

variations

in

needs

Performance

Measures

describe

a

specific

maternal

and

child

need

that

when

effectively

addressed

can

lead

to

improvements

in

health

In

states

completed

the

needs

assessments

and

set

out

priorities

and

targets

for

A

previous

analysis

of

the

priorities

and

measures

found

that

some

states

but

not

all

included

measures

for

preconception

care

or

visits

as

did

Healthy

People

National

Health

Promotion

and

Disease

Prevention

Objectives

-LSB-

-RSB-

Twenty-three

states

reported

a

Priority

Need

that

focused

on

preconception

health

and

health

care

-LRB-

Fig.

-RRB-

Preconception

or

preconceptual

health

was

mentioned

by

states

as

a

Priority

Need

in

maternal

and

child

health

In

other

states

Priority

Needs

indirectly

addressed

preconception

care

via

broad

objectives

such

as

improving

the

health

of

women

of

childbearing

age

promoting

reproductive

health

and

sexual

responsibility

and

advancing

a

holistic

care

continuum

for

women

's

health

A

total

of

states

and

jurisdictions

reported

at

least

one

Performance

Measure

related

to

preconception

care

neural

tube

defects

birth

spacing

family

planning

unintended

pregnancy

and

healthy

weight/obesity

-LRB-

Table

-RRB-

Unintended

pregnancy

and

healthy

weight

or

obesity

were

the

measures

identified

most

frequently

-LRB-

and

respectively

-RRB-

The

majority

of

the

measures

pertaining

to

birth

spacing

or

parity

or

both

addressed

repeat

pregnancies

among

adolescent

populations

A

total

of

thirty

states

or

territories

reported

measures

on

tobacco

use

during

pregnancy

however

only

one

focused

on

the

proportion

of

women

who

smoked

during

months

prior

to

pregnancy

Measures

pertaining

to

smoking

rates

among

women

of

childbearing

age

were

reported

by

two

states

Four

states

addressed

mental

health

among

women

of

childbearing

age

and

postpartum

depression

was

identified

in

three

others

Two

states

included

measures

pertaining

to

preventive

oral

health

services

among

women

of

childbearing

age

-LRB-

data

not

shown

-RRB-

Table

provides

examples

of

selected

State

Performance

Measures

and

Priority

Needs

derived

from

states

Variations

in

state-selected

preconception

health

indicators

are

evident

with

some

states

detailing

various

components

of

preconception

care

and

others

employing

a

broader

focus

on

reproductive

health

Table

or

U.S.

jurisdictions

reporting

Performance

Measures

related

to

selected

preconception

health

topicsPerformance

measureStatePreconception

careNeural

tube

defects/folic

acidBirth

spacing/parityFamily

planningUnintended

pregnancyHealthy

weight/obesityArizona

Arkansas

California

Delaware

District

of

Columbia

a

Florida

aGeorgia

aGuam

Hawaii

Illinois

Indiana

Kentucky

Louisiana

Maine

Marshall

Islands

bMaryland

Massachusetts

Michigan

Minnesota

Mississippi

aMontana

Nebraska

Nevada

New

Jersey

aNew

Mexico

New

York

North

Carolina

North

Dakota

Northern

Mariana

Islands

Ohio

Oklahoma

Puerto

Rico

South

Carolina

TennesseeTexas

South

Dakota

Wyoming

cUtah

Vermont

Washington

bWisconsin

aMeasure

references

repeat

births/pregnancies

among

adolescents

onlybMeasure

references

family

planning

counseling

or

postpartum

birth

control

planning

as

addressed

during

routine

prenatal

carecMeasure

references

multivitamin

use

in

month

prior

to

conceptionTable

of

selected

state

Performance

Measures

and

Priority

Needs

related

to

preconception

healthSelected

performance

measures

and

priority

needsPreconception

health

and

health

care

Performance

measure

Percentage

of

women

of

childbearing

age

who

receive

preconception

health

care

in

the

local

health

department

Priority

need

Enhance

preconception

care

and

work

toward

eliminating

disparities

in

infant

and

maternal

morbidity

and

mortality

Improve

women

's

preconception

and

interconception

health

Improve

indicators

of

health

in

the

preconception

and

perinatal

periods

including

but

not

limited

to

smoking

alcohol

folic

acid

use

family

violence

intention

of

pregnancy

access

to

and

use

of

health

care

Promote

sexual

responsibility

and

reproductive

healthNeural

tube

defects/folic

acid

Performance

Measure

Percent

of

women

of

reproductive

age

who

consume

at

least

mcg

of

folic

acid

daily

Percent

of

women

of

childbearing

age

taking

folic

acid

regularlyBirth

spacing

and

parity

Performance

Measure

Percentage

of

live

births

to

women

who

have

another

birth

in

less

than

months

Percentage

of

repeat

pregnancies

among

adolescents

years

of

age

Priority

need

Reduce

repeat

teenage

pregnancies

unintended

pregnancies

and

inadequate

spacing

of

births

through

widely

available

adequately

funded

comprehensive

efficiently

run

family

planning

and

support

services

Increase

the

proportion

of

births

that

are

intended

including

promotion

of

healthy

interpregnancy

spacingFamily

planning

Performance

measure

Proportion

of

low-income

women

who

receive

reproductive

health/family

planning

services

Priority

need

To

improve

access

to

and

utilization

of

contraceptive

servicesUnintended

pregnancy

Performance

measure

Percentage

of

pregnancies

-LRB-

live

births

fetal

deaths

abortions

-RRB-

that

are

unintended

Percentage

of

women

responding

to

the

Pregnancy

Risk

Assessment

Monitoring

System

-LRB-

PRAMS

-RRB-

survey

that

they

wanted

to

be

pregnant

later

or

not

then

or

at

any

time

in

the

future

Priority

need

Improve

the

health

of

children

and

families

by

increasing

the

percent

of

births

that

are

intended

Promote

planned

pregnancies

and

child

spacingHealthy

weight/obesity

Performance

measure

Percent

of

women

-LRB-

-RRB-

with

healthy

weight

-LRB-

BMI

-RRB-

To

increase

the

percentage

of

Family

Planning

clients

with

BMI

greater

than

the

percentile

who

receive

educational

materials

in

the

Family

Planning

Clinics

and

are

referred

to

community

sources

Priority

need

To

reduce

proportion

of

women

of

childbearing

ages

pregnant

women

and

children

and

youth

with

BMIs

in

the

underweight

overweight

and

obese

categories

Abstracts

from

the

National

Summit

on

Preconception

Care

A

total

of

abstracts

accepted

for

presentation

at

the

National

Summit

on

Preconception

Care

were

reviewed

and

categorized

according

to

primary

area

of

focus

Approximately

addressed

preconception

health

research

described

preconception

care

programs

and

activities

outlined

tools

for

provider

or

patient

education

detailed

clinical

practice

strategies

and

highlighted

policy-based

strategies

for

increasing

access

to

preconception

care

services

Among

the

research

abstracts

the

topics

noted

most

frequently

pertained

to

methods

for

preconception

risk

assessment

potential

predictors

of

adverse

pregnancy

outcomes

and

variations

in

preconception

health

indicators

across

high-risk

populations

Three

abstracts

described

the

use

of

the

Perinatal

Periods

of

Risk

-LRB-

PPOR

-RRB-

model

-LSB-

-RSB-

for

assessing

risks

among

various

populations

Other

issues

included

folic

acid

awareness

among

women

and

health

care

providers

maternal

nutrition

pregnancy

planning

and

risk

behaviors

preconception

hepatitis

B

prevention

and

workplace

hazards

The

PPOR

model

facilitates

the

identification

of

four

contributors

to

infant

mortality

maternal

health

and

prematurity

maternal

care

newborn

care

and

infant

health

Excess

rates

of

fetal

and

infant

mortality

in

any

of

the

four

components

indicate

a

need

for

targeted

interventions

within

that

construct

-LSB-

-RSB-

CityMatCH

's

PPOR

Practice

Collaborative

provided

public

health

workers

in

U.S.

cities

with

the

skills

knowledge

and

support

to

implement

the

PPOR

method

in

various

urban

communities

-LSB-

-RSB-

The

PPOR

approach

is

also

is

being

used

statewide

by

Florida

and

Ohio

and

in

selected

areas

across

the

country

-LSB-

-RSB-

The

Fountain

Project

in

Kansas

City

Missouri

linked

PPOR

techniques

with

the

Fetal

Infant

Mortality

Review

-LRB-

FIMR

-RRB-

process

in

an

effort

to

identify

the

causes

of

consistently

higher

rates

of

infant

mortality

among

African-American

residents

compared

with

their

non-Hispanic

White

counterparts

The

findings

of

the

analysis

indicated

an

excess

rate

of

maternal

health

or

prematurity-related

deaths

among

African-American

infants

In

light

of

the

contributing

social

factors

identified

by

the

FIMR

the

development

of

a

Women

's

and

Children

's

Wellness

Center

was

proposed

to

provide

social

and

clinical

services

for

high-risk

families

-LRB-

Cook

BE

Guillory

VJ

Cai

J

Hoff

GL

Manning

J

unpublished

data

-RRB-

In

an

effort

to

facilitate

the

analysis

of

various

perinatal

health

outcomes

a

group

of

nine

counties

surrounding

the

San

Francisco

Bay

-LRB-

California

-RRB-

formed

the

Maternal

Child

and

Adolescent

Health

Bay

Area

Data

Collaborative

-LRB-

BADC

-RRB-

The

group

used

the

PPOR

model

to

evaluate

recent

county

and

regional

fetal-infant

mortality

rates

and

reported

substantial

excess

in

the

proportion

of

deaths

among

African-American

infants

particularly

in

the

prematurity

and

maternal

health

component

of

the

model

Using

a

national

comparison

group

these

investigators

were

able

to

determine

that

approximately

of

the

excess

deaths

among

African-American

infants

could

be

prevented

by

targeting

preconception

and

interconception

risk

factors

-LRB-

Stein

EJ

Abramowitz

A

Brown

J

Chabra

A

unpublished

data

-RRB-

Federally

funded

Healthy

Start

projects

were

highly

represented

among

the

abstracts

detailing

preconception

care

programs

and

activities

presented

at

the

Summit

Of

these

seven

abstracts

described

the

modification

or

expansion

of

existing

programs

to

include

direct

services

or

community-based

interventions

for

high-risk

postpartum

mothers

or

all

women

of

reproductive

age

The

Magnolia

Project

in

Jacksonville

Florida

is

an

example

of

a

Healthy

Start

program

in

which

a

comprehensive

array

of

health

services

was

offered

in

an

effort

to

improve

birth

outcomes

Services

included

but

were

not

limited

to

case

management

education

and

risk

reduction

and

well-woman

care

The

target

population

was

high-risk

African-American

women

aged

years

who

lived

in

five

zip

code

areas

of

Jacksonville

The

project

operates

as

a

collaborative

between

the

Northeast

Florida

Healthy

Start

Coalition

the

Duval

County

Health

Department

and

local

community-based

organizations

As

reported

a

assessment

of

project

services

conducted

by

the

Health

Resources

and

Services

Administration

-LRB-

HRSA

-RRB-

Office

of

Performance

Review

found

high

rates

of

success

-LRB-

-RRB-

in

the

resolution

of

key

risks

-LRB-

for

example

lack

of

family

planning

and

rates

of

repeat

sexually

transmitted

diseases

-RRB-

among

the

project

participants

-LRB-

Brady

CM

unpublished

data

-RRB-

The

Missouri

Bootheel

Healthy

Start

project

a

provider

of

referral

and

education

services

in

a

five

county

area

of

southeast

Missouri

uses

community-based

education

and

interventions

to

improve

adverse

perinatal

outcomes

The

project

has

been

one

of

few

in

the

area

that

has

promoted

a

family-focused

approach

to

health

education

through

the

inclusion

of

various

services

directed

at

men

The

curriculum

for

fathers

has

addressed

a

variety

of

issues

such

as

communication

with

the

mother

addressing

stress

in

the

relationship

and

the

impact

of

nutrition

on

birth

outcomes

-LRB-

Dean

CG

Campbell

T

Frazier

V

Washington

J

unpublished

data

-RRB-

Title

X

family

planning

clinics

were

identified

as

providers

of

preconception

primary

care

and

folic

acid

awareness

interventions

in

two

programs

and

activities

abstracts

The

Women

Enjoying

Life

Longer

-LRB-

WELL

-RRB-

Project

was

initiated

by

the

Maryland

Department

of

Health

and

Mental

Hygiene

following

a

community

needs

assessment

Comprehensive

preventive

women

's

health

services

were

added

to

three

Title

X

family

planning

clinics

in

Baltimore

County

using

Title

X

and

Maternal

and

Child

Health

funding

Augmented

services

included

nutrition

and

physical

activity

counseling

adult

immunizations

smoking

cessation

interventions

and

preconception

counseling

as

well

as

referrals

for

problems

such

as

substance

abuse

depression

domestic

violence

and

chronic

disease

Early

evaluation

data

indicated

that

patients

and

staff

have

responded

positively

to

new

services

patient

knowledge

of

women

's

health

has

improved

and

patient

volume

has

increased

-LRB-

Cheng

D

unpublished

data

-RRB-

The

Oklahoma

Birth

Defects

Registry

developed

implemented

and

evaluated

a

preconception

women

's

health

appraisal

project

The

intervention

was

comprised

of

a

health

appraisal

for

women

with

follow-up

risk

counseling

in

selected

family

planning

clinics

-LRB-

two

rural

and

one

urban

-RRB-

Pre-evaluation

results

indicated

that

of

nurses

found

the

questionnaire

helpful

in

assessing

risk

factors

of

nurses

found

it

helpful

as

a

guide

to

counseling

and

referrals

and

of

patients

increased

their

understanding

of

risk

factors

Post-evaluation

results

found

that

of

patients

modified

one

to

three

risk

factors

in

a

three-month

period

-LRB-

Feuerborn

VR

Pearson

K

unpublished

data

-RRB-

The

remaining

programs

were

funded

either

through

grants

private

organizations

or

state/local

health

departments

and

comprised

comprehensive

health

care

programs

for

women

with

a

history

of

preterm

delivery

or

a

low

birth

weight

infant

and

broad

women

's

wellness

interventions

aimed

at

improving

women

's

health

or

folic

acid

utilization

For

example

the

Interpregnancy

Care

Program

at

Grady

Memorial

Hospital

in

Atlanta

Georgia

employs

a

resource

mother

to

coordinate

the

provision

of

primary

health

care

and

dental

services

enhanced

nurse

case

management

and

other

outreach

services

to

African-American

women

who

delivered

a

very

low

birth

weight

infant

at

the

hospital

and

who

qualified

for

indigent

or

charity

care

For

months

postpartum

the

women

were

offered

health

care

visits

every

months

in

order

to

address

risks

known

to

be

associated

with

the

delivery

of

a

low

birth

weight

infant

such

as

poorly

controlled

chronic

disease

short

intervals

between

pregnancies

reproductive

tract

infections

periodontal

disease

nutritional

deficits

substance

abuse

and

stress

Preliminary

evaluation

of

the

women

retained

in

the

pilot

program

indicated

that

approximately

one-quarter

of

them

were

affected

by

unrecognized

or

poorly

managed

chronic

health

problems

and

of

the

participants

wanted

to

become

pregnant

during

the

next

years

-LRB-

Dunlop

A

unpublished

data

-RRB-

Thirteen

abstracts

-LRB-

-RRB-

described

the

creation

dissemination

and

evaluation

of

tools

for

patient

or

provider

education

Of

those

eight

described

marketing

campaigns

and

toolkits

for

patient

education

three

specifically

referenced

provider

education

and

three

assessed

the

use

of

women

's

health

appraisals

by

health

care

providers

For

example

the

California

Preconception

Care

Initiative

Every

Woman

Every

Time

was

created

in

through

a

partnership

between

Sutter

Medical

Center

in

Sacramento

and

the

March

of

Dimes

The

project

conducted

a

metanalysis

of

the

preconception

care

literature

-LSB-

-RSB-

and

used

this

information

in

a

consensus

development

process

to

produce

a

marketing

packet

for

providers

Key

components

of

the

packet

included

the

rationale

for

providing

preconception

care

a

description

of

the

essential

elements

of

care

patient

education

materials

and

information

on

billing

methods

More

than

packets

were

distributed

statewide

An

evaluation

found

that

among

providers

responding

indicated

the

information

was

very

useful

said

they

would

distribute

materials

to

patients

and

said

they

would

use

the

billing

codes

provided

A

further

impact

evaluation

is

being

considered

-LRB-

Cullum

AS

unpublished

data

-RRB-

A

research

project

conducted

at

a

New

York

inner-city

hospital

served

by

Albert

Einstein

College

of

Medicine/Montefiore

Medical

Center

sought

to

evaluate

the

knowledge

and

awareness

of

providers

regarding

preconception

care

A

pre-intervention

chart

review

and

a

provider

survey

were

conducted

to

evaluate

delivery

or

preconception

care

The

two-part

intervention

included

-LSB-

-RSB-

a

lecture

for

all

providers

and

-LSB-

-RSB-

a

standardized

preconception

care

form

inserted

into

all

charts

A

post-intervention

chart

review

of

a

convenience

sample

and

repeated

provider

survey

were

then

conducted

The

result

was

a

significant

improvement

in

documentation

of

the

delivery

of

preconception

care

-LRB-

p

-RRB-

however

provider

knowledge

and

attitudes

as

measured

by

the

survey

did

not

change

significantly

-LRB-

Bernstein

P

unpublished

data

-RRB-

Clinical

practice

strategies

were

discussed

in

nine

abstracts

and

included

topics

such

as

genomics

group

care

screening

for

environmental

exposures

and

maternal

depression

smoking

cessation

and

provider

knowledge

of

current

practice

guidelines

An

example

of

a

promising

practice

strategy

presented

at

the

Summit

is

the

use

of

a

group

model

of

prenatal

care

to

address

topics

relevant

to

preconception

care

In

the

Comprehensive

Family

Care

Center

at

Montefiore

Medical

Center

implemented

the

group

model

of

prenatal

care

developed

by

the

Centering

Pregnancy

and

Parenting

Association

Traditional

prenatal

visits

were

replaced

with

group

appointments

lasting

approximately

hours

and

attended

by

women

Typical

clinical

care

services

were

provided

during

the

visits

and

were

supplemented

with

group

discussions

on

pregnancy-related

topics

Issues

related

to

preconception

health

were

covered

during

many

of

the

meetings

and

included

nutrition

substance

abuse

contraception

and

family

planning

Since

its

inception

the

group

care

model

has

been

employed

for

patient

groups

with

high

levels

of

patient

and

provider

satisfaction

reported

particularly

related

to

enhanced

opportunities

for

patient

education

-LRB-

Bernstein

P

Rising

SS

Dolan

S

Pardanani

S

Merkatz

IR

unpublished

data

-RRB-

Finally

policy-based

strategies

for

the

funding

of

preconception

care

were

described

in

a

small

number

of

abstracts

One

pair

of

abstracts

highlighted

Illinois

efforts

to

promote

preconception

health

using

public

policy

and

funding

through

Medicaid

waivers

Title

V

and

other

resources

-LRB-

Murphy

AM

unpublished

data

Saunders

SE

unpublished

data

-RRB-

Identified

as

a

priority

area

preconception

care

has

been

integrated

into

a

number

of

programs

most

notably

the

Illinois

Healthy

Women

program

This

Medicaid

waiver

program

initiative

extends

coverage

for

family

planning

services

to

women

who

would

otherwise

lose

their

benefits

after

days

postpartum

and

to

all

women

through

years

of

age

who

were

previously

enrolled

in

Medicaid

but

who

had

lost

their

benefits

-LRB-

Murphy

AM

unpublished

data

-RRB-

Additional

efforts

have

been

made

through

the

Illinois

Family

Planning

Program

Preconception

education

is

currently

provided

at

all

state-funded

family

planning

clinics

with

state

family

planning

agencies

offering

additional

counseling

and

referral

for

high-risk

clients

-LSB-

-RSB-

Other

strategies

employed

by

the

Illinois

Department

of

Human

Services

include

statewide

genetic

counseling

programs

and

folic

acid

campaigns

screening

mothers

of

children

enrolled

in

the

state

's

Medicaid

program

for

perinatal

depression

and

programs

aimed

at

increasing

birth

spacing

and

promoting

the

health

of

teen

parents

-LRB-

Saunders

SE

unpublished

data

-RRB-

Conclusions

In

public

health

effective

programs

are

those

developed

in

response

to

a

well-defined

problem

analysis

are

mindful

of

the

local

context

and

apply

proven

interventions

Although

the

scientific

evidence

in

support

of

some

preconception

interventions

is

relatively

well

described

within

the

literature

topics

discussed

during

the

National

Summit

on

Preconception

Care

reframed

the

issues

in

light

of

new

findings

regarding

unmet

needs

health

disparities

service

delivery

models

and

tools

such

as

the

PPOR

to

assess

risks

among

populations

Variations

in

the

type

and

scope

of

policies

programs

and

strategies

were

evident

both

in

the

diversity

of

the

summit

abstracts

and

in

the

state

Title

V

indicators

Clearly

a

preconception

focus

is

being

woven

into

existing

programs

and

guiding

the

development

of

new

initiatives

Innovative

strategies

are

being

implemented

that

target

a

variety

of

populations

including

community

groups

health

care

providers

medical

students

adolescents

and

fathers

Finally

many

state

indicators

are

adopting

a

broader

language

to

encompass

the

health

needs

of

women

of

childbearing

age

and

support

the

notion

of

a

lifespan

approach

to

preconception

health

It

should

be

noted

that

the

findings

reported

in

this

brief

are

limited

by

a

number

of

factors

First

state

measures

and

priorities

reported

by

the

federal

Maternal

and

Child

Health

Bureau

might

not

reflect

the

programs

and

projects

actually

being

implemented

by

states

and

communities

they

are

only

an

expression

of

interest

and

concern

Next

the

content

of

the

abstracts

accepted

for

the

National

Summit

on

Preconception

Care

presented

a

selection

of

current

research

policies

and

programs

and

therefore

does

not

fully

represent

the

scope

of

national

preconception

care

projects

Finally

the

identification

of

preconception

health

state

Title

V

indicators

required

a

certain

amount

of

subjective

interpretation

regarding

the

actual

focus

of

the

Priority

Need

or

Performance

Measure

Although

the

authors

have

considerable

knowledge

of

the

definition

and

content

of

preconception

care

it

is

possible

that

certain

indicators

might

have

been

incorrectly

excluded

or

included

due

to

misinterpretation

Notwithstanding

these

limitations

the

results

of

the

present

analysis

indicate

a

widespread

recognition

of

the

need

for

a

continuum

of

care

that

starts

well

before

birth

involves

both

men

and

women

and

employs

a

lifespan

approach

to

emotional

and

physical

well-being

Because

preconception

interventions

can

take

place

at

any

time

during

a

woman

's

reproductive

life

and

across

a

variety

of

dimensions

countless

opportunities

exist

for

positively

influencing

the

health

of

women

children

and

families

The

variations

among

domestic

preconception

health

projects

and

related

public

health

priorities

are

reflective

of

the

true

breadth

of

the

topic

If

a

national

agenda

for

preconception

health

is

to

be

moved

forward

it

is

imperative

that

these

efforts

continue

to

be

fostered

and

expanded

in

all

settings

and

across

a

multitude

of

disciplines

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