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Discovering pathophysiologic networks in a blood-based approach may help to generate valuable tools for early treatment or preventive measures in autism. To date targeted or untargeted metabolomics approaches to identify metabolic features and pathways affecting fetal neurodevelopment have rarely been applied to pregnancy samples, that is, an early period potentially relevant for the development of autism spectrum disorders (ASD). We conducted a population-based study relying on autism diagnoses retrieved from California Department of Developmental Services record. After linking cases to and sampling controls from birth certificates, we retrieved stored maternal mid-pregnancy serum samples collected as part of the California Prenatal Screening Program from the California Biobank for children born 2004 to 2010 in the central valley of California. We retrieved serum for 52 mothers whose children developed autism and 62 population controls originally selected from all eligible children matched by birth year and child's sex. Also, we required that these mothers were relatively low or unexposed to air pollution and select pesticides during early pregnancy. We identified differences in metabolite levels in several metabolic pathways, including glycosphingolipid biosynthesis and metabolism, N-glycan and pyrimidine metabolism, bile acid pathways and, importantly, C21-steroid hormone biosynthesis and metabolism. Disturbances in these pathways have been shown to be relevant for neurodevelopment in rare genetic syndromes or implicated in previous studies of autism. This study provides new insight into maternal mid-pregnancy metabolic features possibly related to the development of autism and an incentive to explore whether these pathways and metabolites are useful for early diagnosis, treatment, or prevention. LAY SUMMARY: This study found that in mid-pregnancy the blood of mothers who give birth to a child that develops autism has some characteristic features that are different from those of blood samples taken from control mothers. These features are related to biologic mechanisms that can affect fetal brain development. In the future, these insights may help identify biomarkers for early autism diagnosis and treatment or preventive measures. Autism Res 2020, 13: 1258-1269. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.

RATIONALE Placenta is a crucial tissue for an appropriate development of the fetus and the course of pregnancy. Its composition and structure change dynamically along pregnancy but the full pattern of these changes is not fully described in cows yet. The aim of the present study was to detect qualitative and quantitative protein profiles of bovine placenta during early-mid pregnancy at the time of placental formation. METHODS Placental tissues from healthy cows (n = 3) in early pregnancy (3-5 months) were collected at the slaughterhouse. Maternal and fetal parts were manually divided prior to homogenization. Further analysis was done in triplicates on the maternal and fetal parts separately and subjected to one-dimensional (1D) electrophoretic separation, followed by identification of peptide maps by nanospray liquid chromatography/tandem mass spectrometry (nanoLC/MS/MS). Proteins were identified by use of the MASCOT software with the SwissProt database. RESULTS Proteomic analysis showed more than 4000 differentially expressed proteins in maternal and fetal parts of placenta. Each part expressed around 900 proteins, of which ca. 90 were common. The identified proteins were analyzed in accordance to molecular function and their participation in biological processes. CONCLUSIONS The obtained results provide new insight into the knowledge about biochemical characteristics of placenta (new proteins) and serve for further studies on the possible markers of physiological/pathological pregnancy or function of placenta. Moreover, our data can be a good starting point for further studies on the processes underlying the attachment of placenta.

Introduction Heavy episodic (“binge”) drinking among women in Scotland is commonplace; prepregnancy drinking is associated with continued antenatal drinking. Evidence for effectiveness of standardized antenatal alcohol assessment is lacking. Alcohol-exposed pregnancies may be missed. We assessed peri-conceptual and mid-pregnancy consumption using a week-long retrospective diary and standard alcohol questionnaires, and evaluated the agreement between these instruments. Material and methods Cross-sectional study in two Scottish health board areas involving 510 women attending mid-pregnancy ultrasound scan clinics. Face-to-face administration of alcohol retrospective diary and AUDIT or AUDIT-C assessed weekly and daily alcohol consumption levels and patterns. Depression-Anxiety-Stress Scale (DASS-21) assessed maternal wellbeing. A sub-sample (n = 30) provided hair for alcohol metabolite analysis. Pearson's correlation coefficient investigated associations between questionnaires and alcohol metabolite data. Results The response rate was 73.8%. The retrospective diary correlated moderately with AUDIT-C and AUDIT but elicited reports of significantly higher peri-conceptual consumption, (median unit consumption on “drinking days” 6.8; range 0.4–63.8). Additional “special occasions” consumption ranged from 1 to 125 units per week. Correlations between DASS-21 and retrospective diary were weak. Biomarker analysis identified three instances of hazardous peri-conceptual drinking. Conclusions Women reported higher consumption levels when completing the retrospective diary, especially regarding peri-conceptual “binge” drinking. Routine clinical practice methods may not capture potentially harmful or irregular drinking patterns. Given the association between prepregnancy and antenatal drinking, and alcohol's known teratogenic effects, particularly in the first trimester, the retrospective diary may be a useful low-tech tool to gather information on alcohol intake patterns and levels.

Introduction Physical activity (PA) is recommended as part of therapy for patients with impaired glucose tolerance. Whether such recommendations are also justified for pregnant women is less well established. We investigated the association between PA and glucose tolerance in pregnancy. Material and methods A non-selective sample of 217 pregnant women was recruited at a routine 20 week ultrasound examination. Participants answered the International Physical Activity Questionnaire (IPAQ) about frequency, intensity and duration of daily physical activity in the past 7 days and underwent oral glucose tolerance testing (OGTT) between 24 and 28 weeks. A subset of 72 overweight/obese pregnant women wore a pedometer for 1 week with assessment of IPAQ score and pedometric correlations to this. Results Of the sample, 177 attended for OGTT; 51% were overweight or obese. The mean (SD) fasting glucose was 4.5 (0.4) mmol/L, and 12% had gestational diabetes mellitus. Only one-third engaged in vigorous PA. After adjustment for pre-pregnancy BMI, age and parity, those engaging in vigorous PA had significantly lower fasting glucose levels (by 0.15 mmol/L, 95% CI 0.03-0.27) compared with those not vigorously active. This decrease was similar in both normal and overweight/obese women. There were fewer cases of gestational diabetes (p = 0.03) among the vigorously active women (3/56; 5%) than among those who were not active (19/121; 16%). No association with glucose tolerance was observed for physical activity of moderate intensity. Conclusions Only vigorous physical activity appears beneficial with respect to maternal glucose tolerance, both among normal, overweight and obese women.

BACKGROUND Folic acid supplementation is recommended for all women of child-bearing age to prevent neural tube defects (NTDs). A nation-wide folic acid supplementation program was implemented in rural areas of China since 2009; however, changes in plasma folate levels in pregnant women were unknown. METHODS A cross-sectional survey was conducted in 2011 to 2012, with 1736 pregnant women enrolled, and results were compared with a previous survey in 2002 to 2004. A microbiological method was used to determine plasma folate levels. Preprogram and postprogram median plasma folate concentrations were compared while stratified by prevalence of NTDs and residence. RESULTS In the high NTD prevalence population, plasma folate concentration increased to 33.4 (18.7, 58.4) nmol/L in the postprogram sample, which is 2.9 times of the preprogram. In the low NTD prevalence population, plasma folate increased to 67.9 (44.5, 101.9) nmol/L, which is 1.9 times of the preprogram. Gaps remained in plasma folate levels with respect to prevalence of NTDs and residence. Folic acid supplementation has a strong impact on plasma folate concentrations. Earlier supplementation (before the last menstrual period), increased supplementation frequency and more total days of supplementation were associated with a higher plasma folate concentration as demonstrated in both the high- and low-prevalence populations. CONCLUSION Plasma folate levels among pregnant Chinese women increased dramatically after the nation-wide folic acid supplementation program in both rural and urban areas, and in populations of high and low NTD prevalence. The nation-wide program should have a component to ensure that supplementation begins before pregnancy. Birth Defects Research (Part A) 103:501–508, 2015. © 2015 Wiley Periodicals, Inc.

Objective This study aimed to assess the accuracy of a second-trimester rapid cervical phosphorylated insulin-like growth factor binding protein-1 (phIGFBP-1) test to predict spontaneous preterm delivery in asymptomatic twin pregnancies. Method During the second trimester, a rapid test to detect phIGFBP-1 in cervical secretions was performed on consecutive twin pregnancies between 2009 and 2011, to evaluate its predictive value for spontaneous preterm delivery at

Objectives The aim of our study was to evaluate placental three-dimensional power Doppler indices in diabetic pregnancies in the second and third trimesters and to compare them with those of the normal controls. Methods Placental vascularization of pregnant women was determined by three-dimensional power Doppler ultrasound technique. The calculated indices included vascularization index (VI), flow index (FI), and vascularization flow index (VFI). Uncomplicated pregnancies (n = 113) were compared with pregnancies complicated by gestational diabetes mellitus (n = 56) and diabetes mellitus (n = 43). Results The three-dimensional power Doppler indices were not significantly different between the two diabetic subgroups. All the indices in diabetic patients were significantly reduced compared with those in non-diabetic individuals (p

Objective The purpose of this study was to describe a series of cases of transient changes in the female fetal external genitalia. Methods In our practice area, most pregnant women usually undergo a detailed sonographic survey of all fetal organs, including the external genitalia in early and mid pregnancy. Results During the study period (1987-2010), 62,145 consecutive pregnant women were scanned. We detected 4 fetuses with an isolated finding of clitoromegaly at 15 to 16 weeks' gestation, which disappeared at 22 to 26 weeks. Maternal hormonal study results were normal. There was 1 case of clitoromegaly and a cloacal anomaly at 15 weeks' gestation, in which the clitoris retuned to a normal size at 22 weeks. In addition, there were 3 cases of hypertrophy of the labia minora in early pregnancy, which disappeared at 26 to 32 weeks. All fetuses in these series had a normal XX karyotype and normal external genitalia at birth. Conclusions Transient changes in the appearance of the fetal external genitalia may occur in chromosomally normal female fetuses.

Objectives To compare the rates of fetal loss, low birth weight, and preterm birth between pregnancies undergoing cordocentesis at mid-pregnancy with placenta penetration and those without it. Methods Consecutive cases of cordocenteses were prospectively recorded. The inclusion criteria for analysis were: (1) singleton pregnancies, (2) no fetal abnormalities, (3) gestational age of 18–22 weeks, and (4) procedures performed by experienced operators. The primary outcome was fetal loss rate, and the secondary outcomes were rates of failed procedures, low birth weight, and preterm birth. Results Of 6147 cordocenteses recorded, 2829 met the inclusion criteria with complete data for analysis. Of these, 654 procedures were further excluded because the puncture site was at cord insertion. The remaining 2175 cases, consisting of 615 procedures with placenta penetration and 1560 cases with no penetration, were analyzed. Cordocenteses with placenta penetration had a significantly higher rate of fetal loss (3.6% vs 1.3%, p = 0.01) as well as of low birth weight and preterm birth. Conclusion Cordocentesis with placenta penetration carries a higher risk for fetal loss, preterm birth, and low birth weight. This information may be helpful in prenatal diagnosis counseling, and it may encourage performers to avoid placenta penetration, if possible. © 2012 John Wiley & Sons, Ltd.

Objective To compare the outcomes after mid-pregnancy cordocentesis between singleton and twin pregnancies. Methods We compared immediate complications and pregnancy outcomes between a cohort of twin pregnancies undergoing mid-pregnancy diagnostic cordocentesis between the years 1989 and 2010, and a control group of singleton pregnancies matched based on maternal age and years of the procedure with a ratio of 1:3. Results Among 6147 pregnancies undergoing cordocentesis during the study period, 122 twin fetuses met the study criteria and were matched with 336 singleton controls. Success rate of sampling was slightly higher in singleton than in twin gestations (98.8% vs 97.3%), and time required for the procedure was significantly longer in the twin group (8.1 vs 6.3 min, p = 0.02). Immediate complications, such as fetal bradycardia and transient bleeding from the puncture site, were significantly higher in twins (13% vs 6.0%, p = 0.001; and 34.8% vs 26.1%, p = 0.03, respectively). However, fetal loss rate within 2 weeks of cordocentesis was not different (1.4% and 1.1%, p = 0.42). Conclusion Immediate complications following cordocentesis are significantly higher in twin pregnancies, but fetal loss rate within 2 weeks of the procedure is comparable. Copyright © 2011 John Wiley & Sons, Ltd.

Objective To evaluate the ability of maternal serum-free β-human chorionic gonadotrophin (β-hCG), pregnancy-associated plasma protein-A (PAPP-A), and alpha fetoprotein (AFP) levels in the screening of fetuses with hemoglobin (Hb) Bart's disease among pregnancies at risk. Materials and Methods Pregnancies at risk for fetal Hb Bart's disease scheduled for cordocentesis at 18 to 22 weeks were recruited into the study. Maternal serum-free β-hCG, PAPP-A, and AFP concentrations were measured before cordocentesis, and the final fetal diagnosis of Hb Bart disease was based on fetal Hb typing using high-performance liquid chromatography. Results Of 57 recruited pregnancies, 11 had fetal Hb Bart's disease and 46 were unaffected. Maternal serum alpha-fetoprotein (MSAFP) concentrations were significantly higher in women with fetal Hb Bart's disease than those with unaffected fetuses (median 99.53 vs 50.83, P < 0.001), whereas the concentrations of free β-hCG and PAPP-A were not significantly different between the two groups (P = 0.543 and 0.777, respectively). Conclusion Second-trimester MSAFP may be clinically a useful screening test for fetal Hb Bart's disease among pregnancies at risk. Copyright © 2011 John Wiley & Sons, Ltd.

A typical late deceleration was observed in a CTG monitoring of a woman in her 23rd week of pregnancy, with preterm labor. The pattern of the deceleration gradually changed to that of early deceleration, and finally disappeared as the pregnancy progressed. Fetal development was normal throughout the pregnancy, and a viable infant was delivered. The significance of late deceleration occurring at mid-term pregnancy may differ from that occurring in late pregnancy, and may reflect physiological development of the fetus at the time.

Objective To study the physiological responses to noninvasive cardiovascular autonomic function tests in normal pregnancy. Design Cardiovascular autonomic responses in 60 women at 22 to 29 weeks gestation and 62 nonpregnant women were investigated using the Valsalva manoeuvre as well as orthostatic, quiet breathing, deep breathing, and isometric handgrip tests. Results Compared with nonpregnant women, those who were pregnant showed significantly lower heart rate variability during normal breathing and a blunted tachycardic reaction to blowing during the Valsalva manoeuvre. The vagally controlled biphasic heart rate response to standing was also attenuated in the pregnant group. Conclusions The cardiovascular responses were blunted in mid-pregnancy indicating a decrease in parasympathetic cardiovascular control.

The effect of conspecific sex on maternal aggression in hamsters was determined by comparing the frequency of aggressive responses by dams continuously housed with either a virgin male or female cagemate during pregnancy and lactation. Dams easily established aggressive dominance over male cagemates soon after pairing, and their aggression was low thereafter for the duration of pregnancy and lactation. The aggression of dams with females, on the other hand, tended to fluctuate with highs during mid pregnancy and mid lactation and lows around birth. When dam aggression was low around birth, female cagemates frequently became aggressively dominant, and several dams lost their litters. The higher aggression of dams toward females than males is probably a reflection of greater intrasexual competition for environmental resources that includes pups.

Summary A group of 497 women whose pregnancies did not exceed 22 weeks and who were booked at the antenatal clinic between 1st August, 1971 and 31st January, 1972 have been included in a survey of arterial pressures in early pregnancy. The arterial pressures showed a low range and confirmed similar previous observations. The blood pressures among the primigravidae in the group were found to be lower than those of their Aberdeen counterparts. It was also found that the arterial pressures were lower than those of comparable non-pregnant women within the same community. The low arterial pressures in early pregnancy did not offer any special advantage in relation to the incidence of pre-eclampsia and eclampsia, diseases known to be prevalent within the community.

Summary The pathways of water exchange between liquor amnii and the fetoplacental unit were examined in vivo in pregnancies of 14 to 22 weeks’gestation. Fetal skin permeability appears to decrease with increasing fetal size while the umbilical cord becomes an increasingly important site from 18 weeks. The fetal surface of the placenta appears to be important as a site of water exchange.