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1.  Fetal endocrinology 
Successful outcome of pregnancy depends upon genetic, cellular, and hormonal interactions, which lead to implantation, placentation, embryonic, and fetal development, parturition and fetal adaptation to extrauterine life. The fetal endocrine system commences development early in gestation and plays a modulating role on the various physiological organ systems and prepares the fetus for life after birth. Our current article provides an overview of the current knowledge of several aspects of this vast field of fetal endocrinology and the role of endocrine system on transition to extrauterine life. We also provide an insight into fetal endocrine adaptations pertinent to various clinically important situations like placental insufficiency and maternal malnutrition.
doi:10.4103/2230-8210.113722
PMCID: PMC3743355  PMID: 23961471
Endocrinology; fetal; hypothalamic; pituitary
2.  Mediators between Theoretical and Practical Medieval Knowledge: Medical Notebooks from the Cairo Genizah and their Significance 
Medical History  2013;57(4):487-515.
This article presents a plethora of fragments from the medical notebooks found in the Cairo Genizah that comprise a unique source of historical data for scholarly study and for a better understanding of the ways in which medieval medical knowledge in Egypt was transferred from theory to practice and vice versa. These documents provide the most direct evidence we have for preferred practical medical recipes because they record the choices of medical practitioners in medieval Cairo. Since the language most commonly used in them was Judaeo-Arabic, they were evidently written by Jews. The medical genre in the notebooks was primarily pharmacopoeic, consisting of apparently original recipes for the treatment of various diseases. There are also a few notebooks on materia medica. The subject matter of the Genizah medical notebooks shows that they were mostly of an eclectic nature, i.e. the writers had probably learnt about these treatments and recipes from their teachers, applied them at the hospitals where they worked or copied them from the books they read. Foremost among the subjects dealt with were eye diseases, followed by skin diseases, coughs and colds, dentistry and oral hygiene, and gynaecological conditions. The writers of the Genizah notebooks apparently recorded the practical medical knowledge they wished to preserve for their future use as amateur physicians, students, traditional healers or professional practitioners.
doi:10.1017/mdh.2013.56
PMCID: PMC3865955  PMID: 24069914
Cairo Genizah; History of Medicine; Jewish; Medieval Middle East; Middle Ages; Notebook
3.  Nonhuman primate models of polycystic ovary syndrome 
With close genomic and phenotypic similarity to humans, nonhuman primate models provide comprehensive epigenetic mimics of polycystic ovary syndrome (PCOS), suggesting early life targeting for prevention. Fetal exposure to testosterone (T), of all nonhuman primate emulations, provides the closest PCOS-like phenotypes, with early-to-mid gestation T-exposed female rhesus monkeys exhibiting adult reproductive, endocrinological and metabolic dysfunctional traits that are co-pathologies of PCOS. Late gestational T exposure, while inducing adult ovarian hyperandrogenism and menstrual abnormalities, has less dysfunctional metabolic accompaniment. Fetal exposures to dihydrotestosterone (DHT) or diethylstilbestrol (DES) suggest androgenic and estrogenic aspects of fetal programming. Neonatal exposure to T produces no PCOS-like outcome, while continuous T treatment of juvenile females causes precocious weight gain and early menarche (high T), or high LH and weight gain (moderate T). Acute T exposure of adult females generates polyfollicular ovaries, while chronic T exposure induces subtle menstrual irregularities without metabolic dysfunction.
doi:10.1016/j.mce.2013.01.013
PMCID: PMC3683573  PMID: 23370180
fetal programming; epigenome; monkey; metabolic syndrome; androgen excess
4.  In memoriam: Celso-Ramon Garcia, M.D. (1922–2004), reproductive medicine visionary 
This article traces the career of Celso-Ramon Garcia (1922–2004), noted physician, educator, and internationally renowned pioneer in the field of reproductive endocrinology. His work helped to formulate oral contraceptives used by millions of women throughout the world. Garcia's research collaborators included Gregory Pincus and John Rock, who together finalized the landmark clinical data needed to secure initial FDA approval for "the pill" in 1960. In addition to Garcia's monumental work in contraceptive endocrinology, his scholarly interests encompassed physiology of the menopause, minimally invasive reproductive surgery, as well as psychological aspects of infertility. Closely identified with the University of Pennsylvania, Garcia was instrumental in establishing the first formal clinical program in reproductive biology and influenced countless young scientists whose training he supervised and mentored. His distinguished career was emblematic of the best of the medical profession, characterized by compassion, intellect, and a sincere desire to help others. Our manuscript outlines Garcia's wide range of interests, acknowledges his superior fund of knowledge, and honors his humanitarian spirit – all of which contributed to an impressive legacy of medical discoveries. The impact of Prof. Garcia's work will continue to be felt for many years.
doi:10.1186/1743-1050-2-2
PMCID: PMC548289  PMID: 15673473
5.  Microbial ecology and host-microbiota interactions during early life stages 
Gut Microbes  2012;3(4):352-365.
The role of human microbiota has been redefined during recent years and its physiological role is now much more important than earlier understood. Intestinal microbial colonization is essential for the maturation of immune system and for the developmental regulation of the intestinal physiology. Alterations in this process of colonization have been shown to predispose and increase the risk to disease later in life. The first contact of neonates with microbes is provided by the maternal microbiota. Moreover, mode of delivery, type of infant feeding and other perinatal factors can influence the establishment of the infant microbiota. Taken into consideration all the available information it could be concluded that the exposure to the adequate microbes early in gestation and neonatal period seems to have a relevant role in health. Maternal microbial environment affects maternal and fetal immune physiology and, of relevance, this interaction with microbes at the fetal-maternal interface could be modulated by specific microbes administered to the pregnant mother. Indeed, probiotic interventions aiming to reduce the risk of immune-mediated diseases may appear effective during early life.
doi:10.4161/gmic.21215
PMCID: PMC3463493  PMID: 22743759
microbiota; early life; infant; health; probiotic
6.  Physiologic assessment of fetal compromise: biomarkers of toxic exposure. 
Understanding the physiologic and endocrinologic basis of fetal development is a major goal of perinatal biology. During the past decade a number of technological developments have allowed more precise evaluation of the fetus in utero and diagnosis of abnormalities. Despite these methodological achievements, however, there are no specific biological markers currently available to indicate that exposure to a given xenobiotic is associated with a cellular, subcellular, or pharmacodynamic event. This paper evaluates the following issues: What are some of the unique physiologic and endocrinologic features of the fetal milieu intérieur? What problems are peculiar to fetal assessment? Of what value are techniques such as ultrasonography, amniocentesis, chorionic villus sampling, fetoscopy, and fetal blood and tissue sampling for obtaining appropriate biomarkers? What are some examples of validated biomarkers and their applicability? What promising biomarkers are on the horizon? What are some of the promising techniques such as the evaluation of fetal body movements, breathing activity, electronic heart rate monitoring, and nuclear magnetic resonance? How may molecular probes be of value as biological markers of fetal compromise? What are some of the major research gaps and needs, and how should research priorities be set? Some of these topics are addressed. Moreover, the more general role(s) that various diagnostic methods and biological markers can have in an understanding of the regulation of fetal growth and differentiation and the role of xenobiotics in affecting the normal course of events are discussed.
PMCID: PMC1474518  PMID: 3319557
7.  Women's Choice of Positions during Labour: Return to the Past or a Modern Way to Give Birth? A Cohort Study in Italy 
BioMed Research International  2014;2014:638093.
Background. Childbirth medicalization has reduced the parturient's opportunity to labour and deliver in a spontaneous position, constricting her to assume the recumbent one. The aim of the study was to compare recumbent and alternative positions in terms of labour process, type of delivery, neonatal wellbeing, and intrapartum fetal head rotation. Methods. We conducted an observational cohort study on women at pregnancy term. Primiparous women with physiological pregnancies and single cephalic fetuses were eligible for the study. We considered data about maternal-general characteristics, labour process, type of delivery, and neonatal wellbeing at birth. Patients were divided into two groups: Group-A if they spent more than 50% of labour in a recumbent position and Group-B when in alternative ones. Results. 225 women were recruited (69 in Group-A and 156 in Group-B). We found significant differences between the groups in terms of labour length, Numeric Rating Scale score and analgesia request rate, type of delivery, need of episiotomy, and fetal occiput rotation. No differences were found in terms of neonatal outcomes. Conclusion. Alternative maternal positioning may positively influence labour process reducing maternal pain, operative vaginal delivery, caesarean section, and episiotomy rate. Women should be encouraged to move and deliver in the most comfortable position.
doi:10.1155/2014/638093
PMCID: PMC4052104  PMID: 24955365
8.  Obstetrics and Gynecology: Considerations in Career Selection 
Western Journal of Medicine  1981;134(1):77-79.
Current training programs in obstetrics and gynecology are not producing an excess of specialists in view of future manpower needs. In addition to being specialists and consultants, obstetrician-gynecologists also function as providers of primary care for women. During the last decade, three formal sub-specialties of obstetrics and gynecology have evolved: gynecologic oncology, maternal-fetal medicine and reproductive endocrinology. These have improved patient care and have altered the structure of resident education. With more American medical school graduates entering this specialty, the quality of resident applicants has improved, creating intense competition for desirable training positions. Those inclined toward a career in obstetrics and gynecology can be assured that it will provide an increasingly favorable and challenging environment for professional activity in the future.
PMCID: PMC1272472  PMID: 7210670
9.  Potential markers of preeclampsia – a review 
Preeclampsia is a leading cause of maternal and fetal/neonatal mortality and morbidity worldwide. The early identification of patients with an increased risk for preeclampsia is therefore one of the most important goals in obstetrics. The availability of highly sensitive and specific physiologic and biochemical markers would allow not only the detection of patients at risk but also permit a close surveillance, an exact diagnosis, timely intervention (e.g. lung maturation), as well as simplified recruitment for future studies looking at therapeutic medications and additional prospective markers. Today, several markers may offer the potential to be used, most likely in a combinatory analysis, as predictors or diagnostic tools. We present here the current knowledge on the biology of preeclampsia and review several biochemical markers which may be used to monitor preeclampsia in a future, that, we hope, is not to distant from today.
doi:10.1186/1477-7827-7-70
PMCID: PMC2717076  PMID: 19602262
10.  Reduced inclination of cervical spine in a novel notebook screen system - implications for rehabilitation 
Background
Professional working at computer notebooks is associated with high requirements on the body posture in the seated position. By the high continuous static muscle stress resulting from this position at notebooks, professionals frequently working at notebooks for long hours are exposed to an increased risk of musculoskeletal complaints. Especially in subjects with back pain, new notebooks should be evaluated with a focus on rehabilitative issues.
Methods
In a field study a new notebook design with adjustable screen was analyzed and compared to standard notebook position.
Results
There are highly significant differences in the visual axis of individuals who are seated in the novel notebook position in comparison to the standard position. Also, differences are present between further alternative notebook positions. Testing of gender and glasses did not reveal influences.
Conclusion
This study demonstrates that notebooks with adjustable screen may be used to improve the posture. Future studies may focus on patients with musculoskeletal diseases.
doi:10.1186/1745-6673-6-30
PMCID: PMC3253038  PMID: 22118159
11.  Gene expression analysis in pregnant women and their infants identifies unique fetal biomarkers that circulate in maternal blood 
The Journal of Clinical Investigation  2007;117(10):3007-3019.
The discovery of fetal mRNA transcripts in the maternal circulation holds great promise for noninvasive prenatal diagnosis. To identify potential fetal biomarkers, we studied whole blood and plasma gene transcripts that were common to 9 term pregnant women and their newborns but absent or reduced in the mothers postpartum. RNA was isolated from peripheral or umbilical blood and hybridized to gene expression arrays. Gene expression, paired Student’s t test, and pathway analyses were performed. In whole blood, 157 gene transcripts met statistical significance. These fetal biomarkers included 27 developmental genes, 5 sensory perception genes, and 22 genes involved in neonatal physiology. Transcripts were predominantly expressed or restricted to the fetus, the embryo, or the neonate. Real-time RT-PCR amplification confirmed the presence of specific gene transcripts; SNP analysis demonstrated the presence of 3 fetal transcripts in maternal antepartum blood. Comparison of whole blood and plasma samples from the same pregnant woman suggested that placental genes are more easily detected in plasma. We conclude that fetal and placental mRNA circulates in the blood of pregnant women. Transcriptional analysis of maternal whole blood identifies a unique set of biologically diverse fetal genes and has a multitude of clinical applications.
doi:10.1172/JCI29959
PMCID: PMC1978418  PMID: 17885688
12.  Impact of maternal body mass index on neonatal outcome 
Introduction
Maternal body mass index has an impact on maternal and fetal pregnancy outcome. An increased maternal BMI is known to be associated with admission of the newborn to a neonatal care unit. The reasons and impact of this admission on fetal outcome, however, are unknown so far.
Objective
The aim of our study was to investigate the impact of maternal BMI on maternal and fetal pregnancy outcome with special focus on the children admitted to a neonatal care unit.
Methods
A cohort of 2049 non-diabetic mothers giving birth in the Charite university hospital was prospectively studied. The impact of maternal BMI on maternal and fetal outcome parameters was tested using multivariate regression analysis. Outcome of children admitted to a neonatal ward (n = 505) was analysed.
Results
Increased maternal BMI was associated with an increased risk for hypertensive complications, peripheral edema, caesarean section, fetal macrosomia and admission of the newborn to a neonatal care unit, whereas decreased BMI was associated with preterm birth and lower birthweight. In the neonatal ward children from obese mothers are characterized by hypoglycaemia. They need less oxygen, and exhibit a shorter stay on the neonatal ward compared to children from normal weight mothers, whereas children from underweight mothers are characterized by lower umbilical blood pH and increased incidence of death corresponding to increased prevalence of preterm birth.
Conclusion
Pregnancy outcome is worst in babies from mothers with low body mass index as compared to healthy weight mothers with respect to increased incidence of preterm birth, lower birth weight and increased neonate mortality on the neonatal ward. We demonstrate that the increased risk for neonatal admission in children from obese mothers does not necessarily indicate severe fetal impairment.
doi:10.1186/2047-783X-14-5-216
PMCID: PMC3351981  PMID: 19541579
maternal BMI; fetal outcome
13.  Using tablets to support self-regulated learning in a longitudinal integrated clerkship 
Medical Education Online  2014;19:10.3402/meo.v19.23638.
Introduction
The need to train physicians committed to learning throughout their careers has prompted medical schools to encourage the development and practice of self-regulated learning by students. Longitudinal integrated clerkships (LICs) require students to exercise self-regulated learning skills. As mobile tools, tablets can potentially support self-regulation among LIC students.
Methods
We provided 15 LIC students with tablet computers with access to the electronic health record (EHR), to track their patient cohort, and a multiplatform online notebook, to support documentation and retrieval of self-identified clinical learning issues. Students received a 1-hour workshop on the relevant features of the tablet and online notebook. Two focus groups with the students were used to evaluate the program, one early and one late in the year and were coded by two raters.
Results
Students used the tablet to support their self-regulated learning in ways that were unique to their learning styles and increased access to resources and utilization of down-time. Students who used the tablet to self-monitor and target learning demonstrated the utility of tablets as learning tools.
Conclusions
LICs are environments rich in opportunity for self-regulated learning. Tablets can enhance students’ ability to develop and employ self-regulatory skills in a clinical context.
doi:10.3402/meo.v19.23638
PMCID: PMC3955768  PMID: 24646438
mobile learning; self-regulated learning; clinical learning; longitudinal integrated clerkship; workplace learning
14.  Molecular mechanisms underlying the fetal programming of adult disease 
Adverse events in utero can be critical in determining quality of life and overall health. It is estimated that up to 50 % of metabolic syndrome diseases can be linked to an adverse fetal environment. However, the mechanisms linking impaired fetal development to these adult diseases remain elusive. This review uncovers some of the molecular mechanisms underlying how normal physiology may be impaired in fetal and postnatal life due to maternal insults in pregnancy. By understanding the mechanisms, which include epigenetic, transcriptional, endoplasmic reticulum (ER) stress, and reactive oxygen species (ROS), we also highlight how intervention in fetal and neonatal life may be able to prevent these diseases long-term.
doi:10.1007/s12079-012-0165-3
PMCID: PMC3421023  PMID: 22623025
Fetal Programming; Epigenetics; microRNA; Posttranslational Histone Modifications; DNA Methylation; ER Stress; Nuclear Receptors
15.  Fetal Surgery 
Canadian Family Physician  1986;32:2099-2103.
Fetal surgery has come of age. For decades experimental fetal surgery proved essential in studying normal fetal physiology and development, and pathophysiology of congenital defects. Clinical fetal surgery started in the 1960s with intrauterine transfusions. In the 1970s, the advent of ultrasonography revolutionized fetal diagnosis and created a therapeutic vacuum. Fetal treatment, medical and surgical, is slowly trying to fill the gap. Most defects detected are best treated after birth, some requiring a modification in the time, mode and place of delivery for optimal obstetrical and neonatal care. Surgical intervention in utero should be considered for malformations that cause progressive damage to the fetus, leading to death or severe morbidity; that can be corrected or palliated in utero with a reasonable expectation of normal postnatal development; that cannot wait to be corrected after birth, even considering pre-term delivery; that are not accompanied by chromosomal or other major anomalies. At present, congenital hydronephrosis is the most common indication for fetal surgery, followed by obstructive hydrocephalus. Congenital diaphragmatic hernia also fulfills the criteria, but its correction poses more problems, and no clinical attempts have been reported so far. In the future many other malformations or diseases may become best treated in utero. The ethical and moral issues are complex and need to be discussed as clinical and experimental progress is made.
PMCID: PMC2328225  PMID: 21267309
fetal surgery; congenital malformations; prenatal diagnosis
16.  Premature rupture of membranes. 
The management of patients with premature rupture of membranes has changed markedly in the past several years. The basis for this is a combination of a better understanding of newborn physiology, improved neonatal care, refinements in antibiotic therapy, and the widespread use of maternal and fetal monitoring. The best outcome for both mother and infant undoubtedly reflects data based on a combination of factors, among which are gestational age survival, evidence of fetal distress, presence or absence of labor and sepsis, and of course, the cervical condition as it is related to labor-readiness. An important recent advance is the recognition that an active observation management program is associated with less morbidity and mortality than the classic management course of delivery within 12 hours of membrane rupture. The fact that preterm premature rupture of membranes tends to recur in subsequent pregnancies offers an opportunity for prevention. Moreover, advances in perinatal and neonatal care will continue to improve the outcomes of these women and their children.
PMCID: PMC2607991  PMID: 8583489
17.  Opiates inhibit paclitaxel uptake by P-glycoprotein in preparations of human placental inside-out vesicles 
Biochemical pharmacology  2009;78(9):1272-1278.
The use of either methadone or buprenorphine for treatment of the pregnant opiate dependent patient improves maternal and neonatal outcome. However, patient outcomes are often complicated by neonatal abstinence syndrome (NAS). The incidence and severity of NAS should depend on opiate concentration in the fetal circulation. Efflux transporters expressed in human placental brush border membranes decrease fetal exposure to medications by their extrusion to the maternal circulation. Accordingly, the concentration of either methadone or buprenorphine in the fetal circulation is, in part, dependent on the activity of the efflux transporters. The objective of this study was to characterize the activity of P-gp and its interaction with opiates in the placental apical membrane. Therefore, brush border membrane vesicles were prepared from human placenta. The vesicles were oriented approximately 75% inside out, exhibited saturable ATP-dependent uptake of P-gp substrate [3H] paclitaxel with an apparent Kt of 66 ± 38 nM and Vmax of 20 ± 3 pmol*mg protein−1min−1. Methadone, buprenorphine, and morphine inhibited paclitaxel transport with apparent Ki of 18, 44, and 90 μM, respectively. Our data indicate that a method has been established to determine the activity of the efflux transporter P-gp, expressed in placental brush border membranes, and the kinetics for the transfer of its prototypic substrate paclitaxel. Furthermore, the method was used to determine the effects of methadone, buprenorphine, and morphine on paclitaxel transfer by placental P-gp and revealed that they have higher affinity to the transporter than its classical inhibitor verapamil (Ki, 300 μM).
doi:10.1016/j.bcp.2009.07.002
PMCID: PMC2748165  PMID: 19591810
Methadone; buprenorphine; placenta; membrane vesicle; p-glycoprotein
18.  Development of PBPK Models for PFOA and PFOS for Human Pregnancy and Lactation Life Stages 
Perfluoroalkyl acid carboxylates and sulfonates (PFAAs) have many consumer and industrial applications. Developmental toxicity studies in animals have raised concern about potential reproductive/developmental effects of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS); however, in humans conflicting results have been reported for associations between maternal PFAA levels and these outcomes. Risk assessments and interpretation of available human data during gestation and lactation are hindered due to lack of a framework for understanding and estimating maternal, fetal, and neonatal pharmacokinetics (PK). Physiologically-based pharmacokinetic (PBPK) models were developed for PFOA & PFOS for the gestation and lactation life stages in humans to understand how the physiological changes associated with development affect pharmacokinetics of these compounds in the mother, fetus, and infant. These models were derived from PBPK models for PFOA/PFOS that were previously developed for adult humans and rats during gestation and lactation and from existing human pregnancy and lactation models developed for other chemicals. The models simulated PFOA and PFOS concentrations in fetal, infant, and maternal plasma and milk, were compared to available data in humans, and also used to estimate maternal exposure. The models reported here identified several research needs, which include: 1) the identification of transporters involved in renal resorption to explain the multi-year half-lives of these compounds in humans, 2) factors affecting clearance of PFOA/PFOS during gestation and lactation, and 3) data to estimate clearance of PFOA/PFOS in infants. These models may help address concerns regarding possible adverse health effects due to PFOA/PFOS exposure in the fetus and infant and may be useful in comparing pharmacokinetics across life stages.
doi:10.1080/15287394.2012.722523
PMCID: PMC3502013  PMID: 23151209
PFOA; PFOS; perfluoroalkyls; gestation; lactation; physiologically based pharmacokinetic model; PBPK
19.  Managing lupus patients during pregnancy 
Best practice & research. Clinical rheumatology  2013;27(3):10.1016/j.berh.2013.07.005.
Systemic lupus erythematosus (SLE) is an autoimmune disease, primarily affecting young females. Pregnancy in a woman with SLE remains a high risk situation with higher maternal and fetal mortality and morbidity. Although live births are achieved in majority of the pregnancies, active disease and major organ involvement can negatively affect the outcomes. Higher risk of fetal loss, pre-term birth, intra-uterine growth restriction and neonatal lupus syndromes are major fetal issues. Mothers are faced with disease flares, pre-eclampsia and other complications. Disease flares during SLE pregnancy pose the unique issue of recognition and differentiation between physiologic changes and disease state. Similarly pre-eclampsia and lupus nephritis may lead to diagnostic confusion. Treatment choices during pregnancy are limited to a few safe drugs, further restricting the options. Refractory pregnancy loss associated with anti-phospholipid antibodies and complete heart block associated with anti-Ro antibodies remain unresolved issues. A multidisciplinary approach, with close monitoring, is essential for optimal outcomes.
doi:10.1016/j.berh.2013.07.005
PMCID: PMC3834352  PMID: 24238698
Systemic lupus erythematosus; anti-phospholipid antibodies; pregnancy; fetal loss; pre-eclampsia; neonatal lupus syndromes
20.  DNA methylation in neonates born to women receiving psychiatric care 
Epigenetics  2012;7(4):409-414.
Prenatal exposure both to maternal psychiatric illness and psychiatric medication has been linked with adverse child outcomes that affect physiological, emotional and psychiatric development. Studies suggest that epigenetic mechanisms, such as DNA methylation, may facilitate these effects. In this report, we explore the association between maternal psychiatric illness and treatment during pregnancy and neonatal DNA methylation patterns in a prospectively-characterized clinical cohort of 201 dyads. Associations between the percent of umbilical cord blood DNA methylated at 27,578 CpG sites and maternal psychiatric diagnosis, symptoms and antidepressant use were evaluated by fitting a separate linear mixed effects model for each CpG site. There were no significant changes in neonatal DNA methylation attributable to maternal psychiatric diagnosis or depressive symptoms during pregnancy. Exposure to an antidepressant medication was associated with differential methylation of CpG sites in TNFRSF21 and CHRNA2 (false discovery rate < 0.05), but the average difference in methylation for both CpG sites was less than 3% between each group. The results were not specific to type of antidepressant or duration of the exposure. This study suggests that there are no large effects of maternal psychiatric illness, depressive symptoms or prenatal exposure to antidepressants on neonatal DNA methylation. Delineation of the influence of maternal psychiatric illness and pharmacological exposures on the developing fetuses has critical implications for clinical care during pregnancy.
doi:10.4161/epi.19551
PMCID: PMC3368823  PMID: 22419064
antidepressants; depressive symptoms; DNA Methylation; HumanMethylation27 BeadChip; Infinium; prenatal exposures
21.  Tertiary care availability and adolescent pregnancy characteristics in Saudi Arabia 
Background
In this study, we aimed to assess the rate of adolescent delivery in a Saudi tertiary health care center and to investigate the association between maternal age and fetal, neonatal, and maternal complications where a professional tertiary medical care service is provided.
Methods
A cross-sectional study was performed between 2005 and 2010 at King Abdulaziz Medical City, Riyadh, Saudi Arabia. All primigravid Saudi women ≥24 weeks gestation, carrying a singleton pregnancy, aged <35 years, and with no chronic medical problems were eligible. Women were divided into three groups based on their age, ie, group 1 (G1) <16 years, group 2 (G2) ≥16 up to 19 years, and group 3 (G3) ≥19 up to 35 years. Data were collected from maternal and neonatal medical records. We calculated the association between the different age groups and maternal characteristics, as well as events and complications during the antenatal period, labor, and delivery.
Results
The rates of adolescent delivery were 20.0 and 16.3 per 1,000 births in 2009 and 2010, respectively. Compared with G1 and G2 women, G3 women tended to have a higher body mass index, a longer first and second stage of labor, more blood loss at delivery, and a longer hospital stay. Compared with G1 and G2 women, respectively, G3 women had a 42% and a 67% increased risk of cesarean section, and had a 52% increased risk of instrumental delivery. G3 women were more likely to develop gestational diabetes or anemia, G2 women had a three-fold increased risk of premature delivery (odds ratio 2.81), and G3 neonates had a 50% increased overall risk of neonatal complications (odds ratio 0.51).
Conclusion
The adolescent birth rate appears to be low in central Saudi Arabia compared with other parts of the world. Excluding preterm delivery, adolescent delivery cared for in a tertiary health care center is not associated with a significantly increased medical risk to the mother, fetus, or neonate. The psychosocial effect of adolescent pregnancy and delivery needs to be assessed.
doi:10.2147/IJWH.S57743
PMCID: PMC3979779  PMID: 24729733
adolescent pregnancy; maternal mortality; maternal morbidity; neonatal mortality; neonatal morbidity
22.  Maternal and Neonatal Circulating Visfatin Concentrations in Patients with Preeclampsia and a Small-For-Gestational Age Neonate 
Objective
Maternal circulating visfatin concentrations are higher in patients with a small-for-gestational-age (SGA) neonate than in those who delivered an appropriate-for-gestational age AGA neonate or in those with preeclampsia. It has been proposed that enhanced transfer of visfatin from the fetal to maternal circulation may account for the high concentrations of maternal visfatin observed in patients with an SGA neonate. The aims of this study were: 1) to determine whether cord blood visfatin concentrations differ between normal neonates, SGA neonates and newborns of preeclamptic mothers; and 2) to assess the relationship between maternal and fetal circulating visfatin concentrations in patients with an SGA neonate and those with preeclampsia.
Study design
This cross-sectional study included 88 pregnant women and their neonates, as well as 22 preterm neonates in the following groups: 1) 44 normal pregnant women at term and their AGA neonates; 2) 22 normotensive pregnant women and their SGA neonates; 3) 22 women with preeclampsia and their neonates; and 4) 22 preterm neonates delivered following spontaneous preterm labor without funisitis or histologic chorioamnionitis, matched for gestational age with infants of preeclamptic mothers. Maternal plasma and cord blood visfatin concentrations were determined by ELISA. Non-parametric statistics were used for analyses.
Results
1) The median visfatin concentration was lower in umbilical cord blood than in maternal circulation, in normal pregnancy, SGA and preeclampsia groups (p<0.001 for all comparisons); 2) the median cord blood visfatin concentrations did not differ significantly between term AGA or SGA neonates, infants of mothers with preeclampsia and their gestational-age-matched preterm AGA neonates; 3) maternal and cord blood visfatin concentrations correlated only in the normal term group (r= 0.48, p=0.04).
Conclusion
Circulating visfatin concentrations are lower in the fetal than in the maternal circulation and did not significantly differ between the study groups. Thus, it is unlikely that the fetal circulation is the source of the high maternal visfatin concentrations reported in patients with an SGA neonate.
doi:10.3109/14767050903572190
PMCID: PMC3413321  PMID: 20121389
visfatin; adipokines; cytokine; pregnancy; fetal growth restriction; AGA; umbilical cord blood
23.  Make it better but don't change anything 
With massive amounts of data being generated in electronic format, there is a need in basic science laboratories to adopt new methods for tracking and analyzing data. An electronic laboratory notebook (ELN) is not just a replacement for a paper lab notebook, it is a new method of storing and organizing data while maintaining the data entry flexibility and legal recording functions of paper notebooks. Paper notebooks are regarded as highly flexible since the user can configure it to store almost anything that can be written or physically pasted onto the pages. However, data retrieval and data sharing from paper notebooks are labor intensive processes and notebooks can be misplaced, a single point of failure that loses all entries in the volume. Additional features provided by electronic notebooks include searchable indices, data sharing, automatic archiving for security against loss and ease of data duplication. Furthermore, ELNs can be tasked with additional functions not commonly found in paper notebooks such as inventory control. While ELNs have been on the market for some time now, adoption of an ELN in academic basic science laboratories has been lagging. Issues that have restrained development and adoption of ELN in research laboratories are the sheer variety and frequency of changes in protocols with a need for the user to control notebook configuration outside the framework of professional IT staff support. In this commentary, we will look at some of the issues and experiences in academic laboratories that have proved challenging in implementing an electronic lab notebook.
doi:10.1186/1759-4499-1-5
PMCID: PMC2810290  PMID: 20098591
24.  Hormonal Evidence Supports the Theory of Selection in Utero 
American Journal of Human Biology  2012;24(4):526-532.
Objectives
Antagonists in the debate over whether the maternal stress response during pregnancy damages or culls fetuses have invoked the theory of selection in utero to support opposing positions. We describe how these opposing arguments arise from the same theory and offer a novel test to discriminate between them. Our test, rooted in reports from population endocrinology that human chorionic gonadotropin (hCG) signals fetal fitness, contributes not only to the debate over the fetal origins of illness, but also to the more basic literature concerned with whether and how natural selection in utero affects contemporary human populations.
Methods
We linked maternal serum hCG measurements from prenatal screening tests with data from the California Department of Public Health birth registry for the years 2001–2007. We used time series analysis to test the association between the number of live born male singletons and median hCG concentration among males in monthly gestational cohorts.
Results
Among the 1.56 million gestations in our analysis, we find that median hCG levels among male survivors of monthly conception cohorts rise as the number of male survivors falls.
Conclusions
Elevated median hCG among relatively small male birth cohorts supports the theory of selection in utero and suggests that the maternal stress response culls cohorts in gestation by raising the fitness criterion for survival to birth.
doi:10.1002/ajhb.22265
PMCID: PMC3372670  PMID: 22411168
hCG; pregnancy; sex ratio; population endocrinology
25.  Do clinical and laboratory parameters effect maternal and fetal outcomes in pregnancies complicated with hemolysis, elevated liver enzymes, and low platelet count syndrome? 
Objective
The aim of the study was to investigate whether the clinical features and laboratory parameters affect maternal and fetal outcomes in pregnancies complicated with HELLP syndrome.
Material and Methods
The medical records of pregnant patients complicated with HELLP syndrome were analyzed retrospectively between June 01, 2003 and June 01, 2010. The demographic data, medical history, admission symptoms, clinical and laboratory findings and recovery time were evaluated. The adverse maternal outcomes including eclampsia, placental abruption, disseminated intravascular coagulation, postpartum hemorrhage, pulmonary complications, cerebral edema and visual loss were recorded. Fetal growth restriction, necessity for neonatal intensive care unit admission and perinatal mortality were recorded as an adverse fetal outcome.
Results
The incidence of HELLP syndrome was 0.52%. The mean age of the patients was 28.93±7.90 (range 17–45). HELLP syndrome was diagnosed on average in the 33.68±4.41th (ranged 24–40) week of gestation. Eighteen cases (40.9%) were nullipara and twenty-six cases (59.1%) multipara. The most common complications were eclampsia (40.9%) and abruption placenta (15.9%). Pregnancy was terminated within 48 hours in all patients. The rate of cesarean section was 90.9%. Perinatal mortality rate in HELLP syndrome was 31.8%. There was no maternal mortality.
Conclusion
Neither clinical characteristics nor laboratory parameters was found effective for prediction of adverse maternal and fetal outcomes.
doi:10.5152/jtgga.2011.68
PMCID: PMC3940217  PMID: 24627667
HELLP syndrome; preeclampsia; maternal outcome; fetal outcome

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