Experimental study of umbilical cord length as a marker of fetal alcohol syndrome

Umbilical cord length has long been investigated as a potential marker of intrauterine events that may place the neonate at risk for future adverse developmental sequelae. Experimentally, significantly shortened cords have been reported in association with prenatal exposure to common drugs of abuse. This study in rats reports the time course of effects on umbilical cord length of a daily maternal ethanol gavage (3,200 mg/kg) from gestational day 6 through termination of pregnancy at either day 17, 18, 19, or 20. A total of 786 fetuses derived from 60 litters were examined. Control fetuses demonstrated a linear increase in umbilical cord length and body weight gain during late gestation, findings that support previous studies. The body weights of the ethanol-exposed fetuses were reduced significantly on all gestational days examined, indicating intrauterine growth retardation, a characteristic of fetal alcohol syndrome. Similarly, acute fetal akinesia as well as long-term sequelae stemming from impaired neurological development would result from the elevated blood ethanol levels achieved in this study. The umbilical cords of ethanol-exposed fetuses were significantly shorter on gestational days 19 and 20 in comparison to their controls, while cord lengths on days 17 and 18 were not shortened significantly. A stretch hypothesis has been proposed suggesting that the degree of fetal activity is the main determinant of umbilical cord length. In rats, there is a physiologic diminution of the volume of amniotic fluid (oligohydramnios) in late gestation (day 19 to term), which restricts fetal movements but does not appear to alter the linear relationships between gestational age and cord length in controls, thus arguing against the stretch hypothesis. However, cord lengths in the ethanol-exposed fetuses plateaued in late gestation, suggesting possible adherence to a stretch hypothesis. This dichotomy is discussed emphasizing fetal growth and activity as well as intrauterine space.     

Ultrasonographic fetometry and prenatal fetal sex assessment in camels (Camelus dromedarius)

The aims of this study were to determine the developmental patterns of some fetal parts to achieve a high accuracy level in the assessment of gestational age and to assess the feasibility and accuracy of ultrasonic prenatal fetal sex assessment in camels. Serial ultrasonographic examinations were carried out on seven pregnant dromedary camels. A total of 329 ultrasonographic examinations were conducted between the second and the 54th weeks of pregnancy. Intrauterine fluid accumulation was detected between the second and third weeks of pregnancy. The embryo proper was noticed between the third and fourth weeks. Organization of the embryo was first observed between the sixth and seventh weeks. Ossification was first detected between the seventh and ninth weeks. The accessibility during the total gestational period was 35/329 (10.6%) for crown-rump length, 35/329 (10.6%) for biparietal diameter, 42/329 (12.8%) for abdominal diameter, 42/329 (12.8%) for ruminal length, and 126/329 (38.3%) for eyeball diameter. A high correlation was found between gestational age and each of the studied parameters (P < 0.0001). The highest correlation was found with the crown-rump length and the biparietal diameter during the first trimester and with the eyeball diameter during the third trimester of pregnancy. The overall accuracy of the ultrasonic prenatal fetal sex assessment was 91.7%. The best window was found during the 11th week of pregnancy. It was concluded that sonographic fetometry can be useful for the evaluation of fetal development, the estimation of gestational age, and the prediction of prenatal fetal sex in camels.     

Use of ultrasound to monitor prenatal growth and development in the common marmoset (Callithrix jacchus)

The increasing use of non-human primates to study fetal development and neonatal management has necessitated the availability of fetuses of known gestational history. In this study, prenatal development and growth were investigated in the common marmoset (Callithrix jacchus) using ultrasound. The objectives of this study were: (1) to determine the accuracy of ultrasound for monitoring prenatal growth and development in common marmosets, (2) to determine if litter size influences prenatal growth trajectories, and (3) to assess growth discordancy among litter mates. Fifty pregnancies were monitored longitudinally using real-time abdominal sonography. During each examination the number of fetuses was recorded, and crown-rump length (CRL) and biparietal diameter (BPD) were measured. The results indicate that ultrasound is a reliable method for observation of gross morphological changes during prenatal development in this species. Measures of CRL and BPD taken early in gestation using ultrasound were in agreement with those from gross specimens. Triplets were significantly (P < 0.05) smaller than twins for both BPD and CRL. No significant relationship was found between litter size and within litter variation in CRL or BPD. This study is the first longitudinal investigation of prenatal growth and development in C. jacchus. The observations from this study will be of use for determining approximate gestational age of fetuses, as well as providing guidelines for routine monitoring of pregnancy in this species. © 1995 Wiley-Liss, Inc.     

Activity of cholinephosphotransferase, lysolecithin: lysolecithin acyltransferase and lysolecithin acyltransferase in the developing mouse lung.

1. The present study presents the activity profiles of cholinephosphotransferase, lysolecithin:lysolecithin acyltransferase and lysolecithin acyltransferase at different stages of development of the mouse lung. 2. The specific activity of cholinephosphotransferase, a key enzyme in the de novo synthesis of phosphatidylcholine, increases during the later stages of fetal development until it reaches a maximal value at a gestational age of 17 days, i.e. 2 days before term. Thereafter, the activity of the enzyme declines again until around term. 2. The specific activity of lysolecithin:lysolecithin acyltransferase which catalyzes the transesterification between two molecules of 1-acyl-sn-glycero-3-phosphocholine, appears to be much lower than that of cholinephosphotransferase at gestational ages below 18 days. However, around day 18, the specific activity of lysolecithin:lysolecithin acyltransferase increases dramatically until it almost equals the maximal activity of cholinephosphotransferase measured on day 17. 4. The specific activity of lysolecithin acyltransferase, which catalyzes the direct acylation of 1-acyl-sn-glycero-3-phosphocholine, does not change significantly during the prenatal development and is lower than that of either lysolecithin:lysolecithin acyltransferase or cholinephosphotransferase at all stages of development. 5. These results are discussed in view of the possible role of these enzymes in the biosynthesis of pulmonary 1,2-dipalmitoyl-sn-glycero-3-phosphocholine.     

Standards of morphological development in fetuses and newborns as a method of defining fetal age

Whenever the calendar age of the studied fetal material is not known we are bound to reconstruct it by replacing it with the developmental age. In this paper some common developmental standards used in the determination of fetal age are reviewed. The standards, as found in the relevant literature, are tested against a control group for their accuracy in predicting fetal age. The results indicate considerable discrepancy among the various standards. Further, the developmental ages defined by these standards often differ considerably from the known menstrual age. My own attempt to present a more reliable set of developmental standards is based on the analysis of three morphological features commonly used in biological assessment. Body weight, crown-heel length, and crown-rump length are measured in weekly termed groups representing the 20th-42nd weeks of intrauterine life. The accuracy of body weight and crown-heel length in predicting fetal age is tested both within and against a control group. Statistical analysis show no significant differences between the predicted and known fetal ages. These results indicate that body weight and crown-heel length are reliable developmental standards from which fetal age can be defined.     

Effects of Prenatal Multiple Micronutrient Supplementation on Fetal Growth Factors: A Cluster-Randomized,Controlled Trial in Rural Bangladesh

Prenatal multiple micronutrient (MM) supplementation improves birth weight through increased fetal growth and gestational age, but whether maternal or fetal growth factors are involved is unclear. Our objective was to examine the effect of prenatal MM supplementation on intrauterine growth factors and the associations between growth factors and birth outcomes in a rural setting in Bangladesh. In a double-blind, cluster-randomized, controlled trial of MM vs. iron and folic acid (IFA) supplementation, we measured placental growth hormone (PGH) at 10 weeks and PGH and human placental lactogen (hPL) at 32 weeks gestation in maternal plasma (n = 396) and insulin, insulin-like growth factor-1 (IGF-1), and IGF binding protein-1 (IGFBP-1) in cord plasma (n = 325). Birth size and gestational age were also assessed. Early pregnancy mean (SD) BMI was 19.5 (2.4) kg/m² and birth weight was 2.68 (0.41) kg. There was no effect of MM on concentrations of maternal hPL or PGH, or cord insulin, IGF-1, or IGFBP-1. However, among pregnancies of female offspring, hPL concentration was higher by 1.1 mg/L in the third trimester (95% CI: 0.2, 2.0 mg/L; p = 0.09 for interaction); and among women with height <145 cm, insulin was higher by 59% (95% CI: 3, 115%; p = 0.05 for interaction) in the MM vs. IFA group. Maternal hPL and cord blood insulin and IGF-1 were positively, and IGFBP-1 was negatively, associated with birth weight z score and other measures of birth size (all p<0.05). IGF-1 was inversely associated with gestational age (p<0.05), but other growth factors were not associated with gestational age or preterm birth. Prenatal MM supplementation had no overall impact on intrauterine growth factors. MM supplementation altered some growth factors differentially by maternal early pregnancy nutritional status and sex of the offspring, but this should be examined in other studies.

Trial Registration

ClinicalTrials.gov NCT00860470     

Correlation between fetal age and ultrasonographic measurements during the second half of pregnancy in domestic cats (Felis catus)

We ultrasonographically evaluated the prenatal development in cats, from Day 30 to the end of pregnancy, subjecting a group of pregnant cats (n = 8) to daily ultrasonographic examinations. The ultrasonographic images allowed us to measure the diameter of the fetal abdomen, the biparietal diameter of the fetal skull and the diameter of the fetal stomach. A correlation between these measurements and gestational age was found with a linear, parabolic and exponential regression analysis. From Days 38 to 43 after breeding we also performed fetal gender determination by evaluating the external genitalia. All queens successfully carried their pregnancies to term. This study compiled useful new data in order to clinically monitor the normal course of pregnancy in cats and to determine gestational age.     

Precision in estimating gestational age and its influence on sensitivity of alphafetoprotein screening.

The interpretation of maternal serum alpha-fetoprotein (AFP) concentrations in relation to fetal neural tube defects depends on accurate assessment of the gestational age. In a quadruple-blind study three antenatal methods of assessment--namely, menstrual dates, clinical examination, and ultrasound scanning--were correlated with postnatal assessment using the Dubowitz scoring system. The best agreement to +/- 1 week was obtained using menstrual dates and ultrasound in combination, such agreement being found in 91 (77%) of the 118 women studied. Since serum AFP concentrations vary with gestational age, precise gestational dating is necessary. In many cases, particularly in women who are unsure of their dates or have irregular menstrual cycles, ultrasound examination is needed to supplement clinical findings.     

Preterm or Not – An Evaluation of Estimates of Gestational Age in a Cohort of Women from Rural Papua New Guinea

BackgroundKnowledge of accurate gestational age is required for comprehensive pregnancy care and is an essential component of research evaluating causes of preterm birth. In industrialised countries gestational age is determined with the help of fetal biometry in early pregnancy. Lack of ultrasound and late presentation to antenatal clinic limits this practice in low-resource settings. Instead, clinical estimators of gestational age are used, but their accuracy remains a matter of debate.MethodsIn a cohort of 688 singleton pregnancies from rural Papua New Guinea, delivery gestational age was calculated from Ballard score, last menstrual period, symphysis-pubis fundal height at first visit and quickening as well as mid- and late pregnancy fetal biometry. Published models using sequential fundal height measurements and corrected last menstrual period to estimate gestational age were also tested. Novel linear models that combined clinical measurements for gestational age estimation were developed. Predictions were compared with the reference early pregnancy ultrasound (<25 gestational weeks) using correlation, regression and Bland-Altman analyses and ranked for their capability to predict preterm birth using the harmonic mean of recall and precision (F-measure).ResultsAverage bias between reference ultrasound and clinical methods ranged from 0–11 days (95% confidence levels: 14–42 days). Preterm birth was best predicted by mid-pregnancy ultrasound (F-measure: 0.72), and neuromuscular Ballard score provided the least reliable preterm birth prediction (F-measure: 0.17). The best clinical methods to predict gestational age and preterm birth were last menstrual period and fundal height (F-measures 0.35). A linear model combining both measures improved prediction of preterm birth (F-measure: 0.58).ConclusionsEstimation of gestational age without ultrasound is prone to significant error. In the absence of ultrasound facilities, last menstrual period and fundal height are among the more reliable clinical measures. This study underlines the importance of strengthening ultrasound facilities and developing novel ways to estimate gestational age.     

Short fetal leukocyte telomere length and preterm prelabor rupture of the membranes

Background

Rupture of the fetal membranes is a common harbinger of imminent labor and delivery. Telomere shortening is a surrogate for oxidative stress (OS) and senescence. Fetal leukocyte and placental membrane DNA telomere lengths were evaluated to determine their association with preterm prelabor rupture of the membranes (pPROM) or spontaneous preterm births with intact membranes (PTB), compared to term birth.

Methods

Telomere lengths were quantified in cord blood leukocytes (n = 133) from three major groups: 1) pPROM (n = 28), 2) PTB (n = 69) and 3) uncomplicated full term births (controls, n = 35), using real-time quantitative PCR. Placental membrane specimens (n = 18) were used to correlate fetal leukocyte and placental telomere lengths. Telomere length differences among the groups were analyzed by ANOVA. Pearson correlation coefficients determined relationships between leukocyte and placental membrane telomere lengths.

Results

In pregnancies with intact membranes, fetal leukocyte telomere length was inversely proportional to gestational age. The mean telomere length decreased as gestation progressed, with the shortest at term. pPROM had telomere lengths (9962±3124 bp) that were significantly shorter than gestational age-matched PTB (11546±4348 bp, p = 0.04), but comparable to term births (9011±2497 bp, p = 0.31). Secondary analyses revealed no effects of race (African American vs. Caucasian) or intraamniotic infection on telomere length. A strong Pearson''s correlation was noted between fetal leukocyte and placental membrane telomere lengths (ρ = 0.77; p<0.01).

Conclusions

Fetal leukocyte telomere length is reduced in pPROM compared to PTB but is similar to term births. pPROM represents a placental membrane disease likely mediated by OS-induced senescence.     

DNA methylation of IGF2, GNASAS,INSIGF and LEP and being born small for gestational age

Being born small for gestational age (SGA), a proxy for intrauterine growth restriction (IUGR) and prenatal famine exposure are both associated with a greater risk of metabolic disease. Both associations have been hypothesized to involve epigenetic mechanisms. We investigated whether prenatal growth restriction early in pregnancy was associated with changes in DNA methylation at loci that were previously shown to be sensitive to early gestational famine exposure. We compared 38 individuals born preterm (<32 weeks) and with a birth weight too low for their gestational age (less than −1SDS; SGA) with 75 individuals born preterm but with a birth weight appropriate for their gestational age (greater than −1SDS) and a normal postnatal growth (greater than −1SDS at three months post term; AGA). The SGA individuals were not only lighter at birth, but also had a smaller length (p = 3.3 × 10⁻¹³) and head circumference at birth (p = 4.1 × 10⁻¹³). The DNA methylation levels of IGF2, GNASAS, INSIGF and LEP were 48.5, 47.5, 79.4 and 25.7% respectively. This was not significantly different between SGA and AGA individuals. Risk factors for being born SGA, including preeclampsia and maternal smoking, were also not associated with DNA methylation at these loci. Growth restriction early in development is not associated with DNA methylation at loci shown to be affected by prenatal famine exposure. Our and previous results by others indicate that prenatal growth restriction and famine exposure may be associated with different epigenetic changes or non-epigenetic mechanisms that may lead to similar later health outcomes.Key words: SGA, DOHAD, IUGR, DNA methylation, famine, IGF2, LEP, INS, GNASAS     

Fetal growth and development of the coypu (Myocastor coypus): Prenatal growth,tooth eruption,and cranial ossification

We examined the fetal growth and development of the coypu (Myocastor coypus), a member of the Caviomorpha that produces extremely precocial young. Analyses of 69 fetuses derived from the latter half of the prenatal period (60–125 days of gestation) focused on external feature growth and development, tooth eruption, and cranial ossification. There were four developmental stages based on morphological characteristics; major external changes predominated over somatic growth in the early stages by 100–105 days of gestation, whereas the last stage was a time of rapid somatic growth. Growth rate was greater in hind foot length (4.3) than in fore foot length (3.4). Soft X-ray photos from 120 to 125 days of gestation show that the incisors, premolars, and first molars were completely calcified, and the second molars were present in the alveolus but not completely calcified. The occlusal surfaces of these teeth were subjected to wear. We analyzed the bone and cartilage of the coypu fetal cranium using a double-staining method. Early ossification of the jugular processes of the occipital bone was a prominent feature of coypu development. The digastric muscle originates on the jugular process, and early ossification should be linked to an adaptation to the herbivorous habit of weaned young coypu. Additionally, the sizes and closure times of six fontanelles are correlated with gestational age and are suggested as a comparative parameter for fetal maturity within and between mammalian species.     

Search for the optimal fetal cell antibody: results of immunophenotyping studies using flow cytometry

Fetal nucleated cells circulating in maternal peripheral blood are a noninvasive source of fetal DNA for prenatal genetic diagnoses. The successful isolation of fetal cells from maternal blood depends upon identification of differences between fetal and maternal cell surface antigen expression. To our best knowledge, a monoclonal antibody that binds only fetal blood cells has not yet been identified. We studied antigens recognized by six different monoclonal antibodies for their biologic expression on fetal blood cells as a function of gestational age, and compared their ability to bind fetal but not maternal cells. The results suggest a relationship between gestational age and nucleated cell surface antigen expression. The monoclonal antibodies FB3-2, H3-3, CD71 and 2-6B/6 are suitable reagents for first or early second trimester fetal cell isolation, although FB3-2 and H3-3 are more specific for fetal cells due to significantly lower expression of these antigens on maternal mononuclear cells. The observation that samples from fetuses with chromosome abnormalities or multiple structural anomalies express higher levels of these antigens indicates that these reagents will potentiate the detection of abnormal fetal cells in maternal blood samples. Received: 23 November 1996 / Accepted: 13 February 1997     

Estimation of gestational age and assessment of canine fetal maturation using radiology and ultrasonography: a review

Since the duration of pregnancy in the bitch is relatively short, it is critical that fetuses are fully mature prior to delivery for them to survive. For breeders to be able to prepare for normal whelpings and align medical care in case of emergency, an estimated due date is necessary. In cases where ovulation timing is lacking and there is a singleton fetus or oversize fetuses, it is necessary to ascertain gestational age prior to setting the date of Cesarean section. In high-risk pregnancies, where there is poor or no ovulation timing, determination of fetal maturation and gestational age will assist in determining if pregnancy has progressed long enough to allow delivery of viable puppies. In cases where bitches are receiving supplemental progesterone for pregnancy maintenance medications must be discontinued at an appropriate time to permit delivery of viable puppies. It also allows for estimation of the likelihood of fetal survival if the pregnancy is terminated due to failing bitch health, with subsequent surgical delivery of the fetuses. Use of breeding dates alone does not provide due dates with adequate accuracy. In cases where there has been inadequate or no breeding management or ovulation timing, estimation of due date can be performed at the time of pregnancy diagnosis, or closer to term. Radiography can be used to confirm pregnancy and facilitate determination of gestational age, beginning 45d after the LH surge. Ultrasonography can be used from 19 to 21d after the LH surge to term to confirm pregnancy and predict gestational age, and from 25 or 26d to term to assess fetal viability and fetal stress.     

Maternal Prenatal Positive Affect,Depressive and Anxiety Symptoms and Birth Outcomes: The PREDO Study

Background

We investigated whether maternal prenatal emotions are associated with gestational length and birth weight in the large PREDO Study with multiple measurement points of emotions during gestation.

Methods

Altogether 3376 pregnant women self-assessed their positive affect (PA, Positive and Negative Affect Schedule) and depressive (Center for Epidemiologic Studies Depression Scale, CES-D) and anxiety (Spielberger State Anxiety Scale, STAI) symptoms up to 14 times during gestation. Birth characteristics were derived from the National Birth Register and from medical records.

Results

One standard deviation (SD) unit higher PA during the third pregnancy trimester was associated with a 0.05 SD unit longer gestational length, whereas one SD unit higher CES-D and STAI scores during the third trimester were associated with 0.04–0.05 SD unit shorter gestational lengths (P-values ≤ 0.02), corresponding to only 0.1–0.2% of the variation in gestational length. Higher PA during the third trimester was associated with a significantly decreased risk for preterm (< 37 weeks) delivery (for each SD unit higher positive affect, odds ratio was 0.8-fold (P = 0.02). Mothers with preterm delivery showed a decline in PA and an increase in CES-D and STAI during eight weeks prior to delivery. Post-term birth (≥ 42 weeks), birth weight and fetal growth were not associated with maternal prenatal emotions.

Conclusions

This study with 14 measurements of maternal emotions during pregnancy show modest effects of prenatal emotions during the third pregnancy trimester, particularly in the weeks close to delivery, on gestational length. From the clinical perspective, the effects were negligible. No associations were detected between prenatal emotions and birth weight.     

Advances in ultrasound imaging for congenital malformations during early gestation

BACKGROUND : With refinement in ultrasound technology, detection of fetal structural abnormalities has improved and there have been detailed reports of the natural history and expected outcomes for many anomalies. The ability to either reassure a high‐risk woman with normal intrauterine images or offer comprehensive counseling and offer options in cases of strongly suspected lethal or major malformations has shifted prenatal diagnoses to the earliest possible gestational age. METHODS : When indicated, scans in early gestation are valuable in accurate gestational dating. Stricter sonographic criteria for early nonviability guard against unnecessary intervention. Most birth defects are without known risk factors, and detection of certain malformations is possible in the late first trimester. RESULTS : The best time for a standard complete fetal and placental scan is 18 to 20 weeks. In addition, certain soft anatomic markers provide clues to chromosomal aneuploidy risk. Maternal obesity and multifetal pregnancies are now more common and further limit early gestation visibility. CONCLUSION : Other advanced imaging techniques during early gestation in select cases of suspected malformations include fetal echocardiography and magnetic resonance imaging. Birth Defects Research (Part A) 103:260–268, 2015. © 2015 Wiley Periodicals, Inc.     

Medium chain fatty acids in intrauterine growth restricted and small for gestational age pregnancies

Introduction

Low birth weight is associated with an increased risk of heart disease, high blood pressure and diabetes in adult life. Fetal growth is determined by nutrient availability, which is related to placenta nutrient transport. Medium chain fatty acids (MCFAs) are a particular class of nutrients, known to be a readily available energy source. Until now no data are reported on these MCFAs in low birth weight fetus.

Aim

This is a prospective study conducted in a tertiary center of prenatal diagnosis to investigate the maternal and fetal MCFAs levels in appropriate for gestational age (AGA), intrauterine growth restricted (IUGR), and small for gestational age (SGA) pregnancies.

Method

The plasmatic levels of MCFAs in AGA, IUGR and SGA mother–infant pairs were quantified by gas chromatography–mass spectrometry. The analytical method had a linearity range of 0.1–50 mg/L and a limit of quantification of 0.03 mg/L. Reduced fetal growth was defined as an estimated fetal weight below the 3rd–10th percentile for gestational age, with (IUGR) or without (SGA) fetal Doppler abnormalities.

Result

Maternal and fetal MCFAs plasma levels were significantly different among SGA, IUGR and AGA groups. Additionally, the observed MCFAs fetal to maternal ratio is >1 for IUGR group, whilst for SGA and AGA the fetal to maternal ratio is less than one.

Conclusion

Changes in MCFAs levels in fetal and maternal plasma are not related to placental functionality or nutrients availability, suggesting the presence of a de novo biosynthesis.

     

DNA methylation of IGF2, GNASAS,INSIGF and LEP and being born small for gestational age

Being born small for gestational age (SGA), a proxy for intrauterine growth restriction (IUGR), and prenatal famine exposure are both associated with a greater risk of metabolic disease. Both associations have been hypothesized to involve epigenetic mechanisms. We investigated whether prenatal growth restriction early in pregnancy was associated with changes in DNA methylation at loci that were previously shown to be sensitive to early gestational famine exposure. We compared 38 individuals born preterm (&lt;32 weeks) and with a birth weight too low for their gestational age (-1SDS) and a normal postnatal growth (>-1SDS at 3 months post term; “AGA”). The SGA individuals were not only lighter at birth, but also had a smaller length (P=3.3x10^-13) and head circumference at birth (P=4.1x10^-13). The DNA methylation levels of IGF2, GNASAS, INSIGF and LEP were 48.5%, 47.5%, 79.4% and 25.7% respectively. This was not significantly different between SGA and AGA individuals. Risk factors for being born SGA, including preeclampsia and maternal smoking, were also not associated with DNA methylation at these loci. Growth restriction early in development is not associated with DNA methylation at loci shown to be affected by prenatal famine exposure. Our and previous results by others indicate that prenatal growth restriction and famine exposure may be associated with different epigenetic changes or non epigenetic mechanisms that may lead to similar later health outcomes.     

Prenatal Glucocorticoid Treatment and Later Mental Health in Children and Adolescents

Background

Animal studies demonstrate a clear link between prenatal exposure to glucocorticoids (GC) and altered offspring brain development. We aim to examine whether prenatal GC exposure programs long-term mental health in humans.

Methods

Using propensity-score-matching, children prenatally exposed to synthetic glucocorticoids (sGC), n=37, and controls, n=185, were balanced on important confounders related to sGC treatment - gestational age and pre-pregnancy BMI. We also used mixed-effects modeling to analyse the entire cohort – matching each sGC case, n=37, to all possible controls, n=6079, on gestational age and sex. We obtained data from the Northern Finland Birth Cohort 1986 at four waves – pregnancy, birth, 8 and 16 years. Data on pregnancy and birth outcomes came from medical records. Mental health was assessed at 8 years by teachers with the Rutter B2 scale, and at 16 years by parents with the Strengths and Weaknesses of ADHD symptoms and Normal behavior (SWAN) scale and adolescents by the Youth Self-Report (YSR) scale.

Results

Prenatal sGC treatment was consistently associated with adverse mental health in childhood and adolescence, as shown by both the propensity-score method and mixed-effects model. Using the propensity-score-matched subsample, linear multiple regression showed prenatal sGC was significantly linked with general psychiatric disturbance (B=8.34 [95% CI: .23-16.45]) and inattention (B= .97 [95% CI: .16-1.80]) at 8 years after control for relevant confounders. Similar findings were obtained at 16 years, but did not reach statistical significance. Mediation by birthweight/placental weight was not detected.

Conclusions

This study is the first to prospectively investigate the long-term associations between prenatal exposure to sGC treatment and mental health in children and adolescents. We report an association between prenatal exposure to sGC and child mental health, supportive of the idea that sGC has a programming effect on the fetal brain.