Clinical associations of fetal heart rate accelerations as derived from transabdominal fetal electrocardiograms.

OBJECTIVE: To determine the value of quantifying accelerations of the fetal heart rate (FHR), as collected non-invasively during pregnancy, as a proxy for fetal movements. STUDY DESIGN: The study consists of a prospective collection of research material with retrospective analyses of the collected fetal electrocardiograms (ECGs), done in a homogeneous population in a low socioeconomic residential area of Cape Town, South Africa, as part of the Safe Passage Study. Recruitment and follow-up were done from August 2007 to August 2016. Maternal and fetal ECGs were collected non-invasively at various gestational ages, for approximately 30-60 min at a time in 4418 pregnant women. After processing of the signal, the number and duration of accelerations and the area under the acceleration curve of the FHR were calculated and compared with the pulsatility index (PI) of the uterine, umbilical, and middle cerebral arteries, common medical conditions, tobacco, alcohol, marijuana, and methamphetamine use and z-scores of the birthweight (BWZS). RESULTS: Of the total, 2777, 691, and 3879 women were at gestational ages of 20-24, 28-32 and 34-38 weeks respectively. At 20-24 weeks duration of accelerations was significantly longer in women who used marijuana (p = 0.014) or methamphetamine (p < 0.001) when compared to nonusers. At 28-32 weeks the duration of accelerations was significantly shorter in hypertensive women (p = 0.003) and significantly longer in women who used methamphetamine (p = 0.015). At 34-38 weeks the number of accelerations were significantly less in women who had hypertension ((p = 0.01) or stillbirths (p = 0.028) and the duration significantly shorter in hypertensive women (p = 0.007) and significantly longer in women who used marjuana (p = 0.003) or methamphetamine (p = 0.028). The acceleration area was significantly smaller (p = 0.02) in women who has stillbirths. Duration of accelerations was significantly longer in users of nicotine and alcohol when compared with that of abstainers. Birthweight z-score correlated significantly with number of accelerations (p < 0.01) and the acceleration area (<0.01). There was a significant negative correlation between the number of accelerations (p < 0.01) and acceleration area (p < 0.01) and the PI of the uterine artery at 34-38 weeks. CONCLUSIONS: Calculation of the acceleration parameters of the FHR during pregnancy may provide useful information for evaluating fetal development.

The tragedy of smoking, alcohol, and multiple substance use during pregnancy.

BACKGROUND: Antenatal substance use is a significant public health concern in South Africa (SA). Information on smoking, drinking and drug use during pregnancy was collected prospectively for the Safe Passage Study of the PASS (Prenatal Alcohol in Sudden infant death syndrome and Stillbirth) Network. OBJECTIVES: Data from 4 926 pregnant women in a community near Tygerberg Academic Hospital, Cape Town, were examined to determine whether associations between different substance use groups and postnatal infant outcomes at birth and 1 year were significant. METHODS: Gestational age (GA) was determined by earliest ultrasound. Maternal data were collected at enrolment or first antenatal visit. Substance use data were obtained at up to four occasions. Birthweight data were derived from medical records, and birthweight z-scores (BWZs) were specifically calculated using INTERGROWTH-21st study data. Statistical analyses were done with Statistica version 13.  Results. Women who used more substances enrolled later, were younger, and had smaller mid-upper arm circumferences (MUACs), less education and lower monthly income than women who used no substances (control group). Infants born to women who used more substances had lower GA at delivery, birthweight and BWZ than infants from the control group. At 1 year, infants born to women who used more substances had a lower weight, shorter length and smaller head circumference. Education was positively associated with all infant outcomes at birth and 1 year. MUAC was positively associated with infant BWZ, and weight and length at 1 year. Income was negatively associated with BWZ, but positively associated with all 1-year outcomes. CONCLUSION: Substance use during pregnancy affects infant outcomes at birth and 1 year of age. The addictive properties of substance use make cessation difficult, so prevention strategies should be implemented long before pregnancy. Higher maternal education, associated with better infant outcomes at birth and 1 year and acting as a countermeasure to substance use, is of paramount importance.

Classification of intrauterine growth restriction at 34-38 weeks gestation with machine learning models.

OBJECTIVE: Intrauterine growth restriction (IUGR) is one of the most common causes of stillbirths. The objective of this study is to develop a machine learning model that will be able to accurately and consistently predict whether the estimated fetal weight (EFW) will be below the 10th percentile at 34+0-37 + 6 week's gestation stage, by using data collected at 20 + 0 to 23 + 6 weeks gestation. METHODS: Recruitment for the prospective Safe Passage Study (SPS) was done over 7.5 years (2007-2015). An essential part of the fetal assessment was the non-invasive transabdominal recording of the maternal and fetal electrocardiograms as well as the performance of an ultrasound examination for Doppler flow velocity waveforms and fetal biometry at 20 + 0 to 23 + 6 and 34 + 0 to 37 + 6 week's gestation. Several predictive models were constructed, using supervised learning techniques, and evaluated using the Stochastic Gradient Descent, k-Nearest Neighbours, Logistic Regression and Random Forest methods. RESULTS: The final model performed exceptionally well across all evaluation metrics, particularly so for the Stochastic Gradient Descent method: achieving a 93% average for Classification Accuracy, Recall, Precision and F1-Score when random sampling is used and 91% for cross-validation (both methods using a 95% confidence interval). Furthermore, the model identifies the Umbilical Artery Pulsality Index to be the strongest identifier for the prediction of IUGR - matching the literature. Three of the four evaluation methods used achieved above 90% for both True Negative and True Positive results. The ROC Analysis showed a very strong True Positive rate (y-axis) for both target attribute outcomes - AUC value of 0.771. CONCLUSIONS: The model performs exceptionally well in all evaluation metrics, showing robustness and flexibility as a predictive model for the binary target attribute of IUGR. This accuracy is likely due to the value added by the pre-processed features regarding the fetal gained beats and accelerations, something otherwise absent from previous multi-disciplinary studies. The success of the proposed predictive model allows the pursuit of further birth-related anomalies, providing a foundation for more complex models and lesser-researched subject matter. The data available for this model was a vital part of its success but might also become a limiting factor for further analyses. Further development of similar models could result in better classification performance even with little data available.

The Association between Maternal Depression, Infant Characteristics and Need for Assistance in A Low-Income-Country.

Background: Depression in the peripartum period is prevalent in low-income-countries. The identification of women needing referral is often lacking and on the other hand, women in need of support and treatment do not make use of existing support. Objectives: To identify risk factors for fetal and postnatal consequences of depression in pregnancy and to investigate further management once women at risk have been identified. Methods: The Safe Passage Study was a large prospective multicenter international study. Extensive information, including the Edinburgh postnatal depression scale (EPDS), was collected during the study. At risk women were referred to the study's social worker (SW). Women were categorized according to risk on their EPDS results. Risk categories were characterized and investigated for infant outcomes. Results: Data from 5,489 women were available for analysis and revealed a 51% prevalence of prenatal depression. Fourteen percent of at-risk women attended SW appointments, while 36% accepted the SW referral but persistently failed to attend. At risk women were significantly younger, had less formal education, had lower monthly income, and lived in more crowded conditions. They used significantly more alcohol and cigarettes. Their infants had shorter gestational ages, lower birth weights and were more growth restricted. Infants of depressed women who missed appointments weighed less and were more growth restricted. Conclusion: Women with high EPDSs had less favorable socioeconomic conditions, used more alcohol or tobacco during pregnancy, and their infants weighed less with more growth restriction. Women who repeatedly missed their appointments came from the poorest socioeconomic conditions and their infants had worse birth outcomes.

In utero teratogen exposure and cardiometabolic risk in 5-year-old children: a prospective pediatric study.

BACKGROUND: Aorta and carotid intima-media thickness (IMT) is a measure of subclinical atherosclerosis and useful to assess cardiometabolic risk in the young. The in utero milieu may involve cardiometabolic programing and the development of cardiometabolic risk factors in children. Maternal smoking, alcohol consumption, and micronutrient deficiencies during pregnancy influence the development of the cardiovascular system through a process of DNA methylation. AIM: To explore an association between maternal smoking and alcohol consumption during pregnancy and intima media thickness in 5-year-old children for a low-income setting. METHODS: Data were collected from 500 mother-child pairs at antenatal clinic visit, at birth, and at age 5 years. Anthropometric measurements were collected at birth and again at age 5 years. As well as clinical and ultrasound measurements at age 5 years. Clinical measurements, at age 5 years, included blood pressure, mean arterial pressure, and heart rate. Ultrasound measurements of the aorta and carotid arteries IMT were performed at age 5 years. Main outcome of interest was effect of dual teratogen exposure on the ultrasound measures IMT as indication of cardiometabolic risk. RESULTS: cIMT was significantly higher in children exposed to both alcohol and nicotine during pregnancy compared to those not exposed (p = .008). In separate linear models, dual in utero exposure (beta = 0.12; p = .01) and male sex (beta = 0.14; p = .01) were associated with higher right cIMT values (F(6,445) = 5.20; R2 = 0.07, p < .01); male sex (beta = 0.13; p = .01) and low birth weight (beta = 0.07; p = .01) with higher left cIMT value (F(4,491) = 4.49; R2 = 0.04; p = .01); and males sex (beta = 0.11; p = .02) with higher aorta IMT (F(6,459) = 5.63; R2 = 0.07; p < .01). Significant positive correlations between maternal measures of adiposity, maternal MUAC (r = 0.10; p = .03), and maternal BMI (r = 0.12; p < .01) and right cIMT measurements adjusted for the BMI of the child at age 5 years as covariate. Blood pressure measurements at age 5 years were not significantly associated with IMT but, instead, correlated significantly and positively with the BMI of the child at age 5 years (p < .01). CONCLUSION: Children exposed to both maternal smoking and alcohol consumption during pregnancy presented with cardiometabolic risk factors 5 years after birth. In addition, maternal adiposity, male sex, and low birth weight were associated with higher IMT at age 5 years.

The effects of in utero exposure to teratogens on organ size: a prospective paediatric study.

In low-income countries, prospective data on combined effects of in utero teratogen exposure are lacking and necessitates new research. The aim of the present study was to explore the effect of in utero teratogen exposure on the size of the kidneys and pancreas 5 years after birth in a low-income paediatric population. Data was collected from 500 mother-child pairs from a low-income setting. Anthropometric measurements included body weight, (BW) body height, mid-upper arm and waist circumference (WC). Clinical measurements included blood pressure (BP), mean arterial pressure and heart rate. Ultrasound measurements included pancreas, and kidney measurements at age 5 years. The main outcome of interest was the effect of maternal smoking and alcohol consumption on ultrasound measurements of organ size at age 5 years. Left and right kidney length measurements were significantly lower in smoking exposed children compared to controls (p = 0.04 and p = 0.03). Pancreas body measurements were significantly lower in smoking exposed children (p = 0.04). Multiple regression analyses were used to examine the associations between the independent variables (IDVs), maternal age, body mass index (BMI), mid-upper arm circumference (MUAC) and BW of the child, on the dependent variables (DVs) kidney lengths and kidney volumes. Also, the association between in utero exposure to alcohol and nicotine and pancreas size. WC was strongest (r = 0.28; p < 0.01) associated with pancreas head [F (4, 454) = 13.44; R2 = 0.11; p < 0.01] and tail (r = 0.30; p < 0.01) measurements at age 5 years, with in utero exposure, sex of the child and BMI as covariates. Kidney length and pancreas body measurements are affected by in utero exposure to nicotine at age 5 years and might contribute to cardiometabolic risk in later life. Also, findings from this study report on ultrasound reference values for kidney and pancreas measurements of children at age 5 years from a low-income setting.

Smoking and drinking habits of women in subsequent pregnancies after specific advice about the dangers of these exposures during pregnancy.

BACKGROUND: Although women are informed about the dangers of drinking and smoking during pregnancy when they book for antenatal care, it is uncertain whether this advice is accepted, or whether attempts are made to apply it in subsequent pregnancies. OBJECTIVES: To assess how pregnant women respond to the advice to refrain from smoking and drinking during pregnancy in subsequent pregnancies. METHODS: Research staff were trained to obtain accurate prospective information on smoking and drinking during pregnancy in a prospective study, using well-standardised methods. Care was taken to inform participants about the dangers of smoking and drinking during pregnancy. They were also given pamphlets on these dangers in their own language and a list of telephone numbers where they could find help to quit should they need it. This information was repeated at subsequent study visits (ranging from 1 to 3, depending on the gestational age at which they enrolled). Gestational age was determined by early ultrasound. Z-scores of birthweight for gestational age were determined according to the INTERGROWTH-21st study. Pregnancy outcomes of women who enrolled twice (n=888) or three times (n=77) in the Safe Passage Study were compared with those of women in the first enrolment (n=889). RESULTS: The proportion of drinkers did not change significantly (p=0.058) from the first to the second and third enrolments (63.8%, 59.0% and 54.6%, respectively). A similar trend was found for smokers (73.3%, 72.2% and 68.4%, respectively). Cannabis use was reported by 15.1%, 9.7% and 12.0% (p<0.005) of women, respectively, and use of methamphetamine by 10.1%, 6.6% and 12.7% (p<0.005). There was an increase in the rate of preterm births from 15.5% to 17.5% and 24.7%, respectively, but the increase was not significant. Although mean birthweight was lower in the third enrolment compared with the second, the difference was not significant. The z-score of birthweight for gestational age was significantly lower in the second enrolment compared with the first. CONCLUSIONS: Detailed information on the adverse effects of smoking and drinking during pregnancy was not effective in the population studied. Other methods to reduce or stop these toxic exposures should therefore be investigated. A short inter-pregnancy interval, as demonstrated by three enrolments in 7.5 years, is associated with preterm labour and fetal growth restriction, and is probably indicative of the role played by confounders such as poor socioeconomic conditions and drug exposure during pregnancy.

The association between preterm labour, perinatal mortality and infant death (during the first year) in Bishop Lavis, Cape Town, South Africa.

BACKGROUND: We present further analyses from the Safe Passage Study, where the effect of alcohol exposure during pregnancy on sudden infant death syndrome and stillbirth was investigated. OBJECTIVES: To describe pregnancy and neonatal outcome in a large prospective study where information on the outcome of pregnancy was known in >98.3% of participants and ultrasound was used to determine gestational age (GA). METHODS: As part of the Safe Passage Study of the PASS Network in Cape Town, South Africa, the outcomes of 6 866 singleton pregnancies were prospectively followed from recruitment in early pregnancy until the infant was 12 months old to assess pregnancy outcome. Fetal growth was assessed by z-scores of the birth weight, and GA at birth was derived from early ultrasound assessments. The effects of fetal growth restriction and preterm delivery on pregnancy outcome were determined. RESULTS: There were 66 miscarriages, 107 stillbirths at ≥22 weeks' gestation, 66 stillbirths at ≥28 weeks' gestation, 29 and 18 neonatal deaths at ≥22 and ≥28 weeks' gestation, respectively, and 54 post-neonatal deaths (28 days - 12 months). The miscarriage rate was 9.6/1 000 and the infant mortality rate 12.4/1 000. Of the births, 13.8% were preterm. For deliveries at ≥22 and ≥28 weeks, the stillbirth rates were 15.7 and 9.8/1 000 deliveries, respectively. For deliveries at ≥22 and ≥28 weeks, the neonatal death rates were 4.3 and 2.7/1 000 live births, respectively. For these pregnancies the perinatal mortality rates were 20.0/1 000 (≥22 weeks) and 12.5/1 000 (≥28 weeks), respectively. Only 15.9% of stillbirths occurred during labour (in 15.9% of cases it was uncertain whether death had occurred during labour). In the majority of cases (68.2%) fetal death occurred before labour, and 82.2% of stillbirths and 62.1% of neonatal deaths occurred in deliveries before 37 weeks. Including the miscarriages, stillbirths and infant deaths, there were 256 pregnancy losses; 77.3% were associated with deliveries before 37 weeks. Only 1.8% of all the women were HIV-positive, whereas the HIV-positive rate was 3.7% among those who had stillbirths. Birth weight was below the 10th centile in 25.6% of neonatal and post-neonatal deaths compared with 17.7% of survivors. CONCLUSIONS: Preterm birth and fetal growth restriction play significant roles in fetal, neonatal and infant losses.

Effects of alcohol, cigarettes, methamphetamine and marijuana exposure during pregnancy on maternal serum alpha-fetoprotein levels at 20-24 weeks'gestation.

OBJECTIVE: To examine the effects of cigarette, marihuana and methamphetamine smoking and consumption of alcohol during pregnancy on maternal serum alpha-fetoprotein (MSAFP) levels at 20-24 weeks. STUDY DESIGN: In the Safe Passage Study (SPS) more than 12,000 pregnant women were prospectively followed up during pregnancy and until the infant was one year old to examine the effects of exposure to alcohol during pregnancy on stillbirth and sudden infant death syndrome. The present study is a cross-sectional secondary analysis of MSAFP analyses done at 20-24 weeks gestation in 1,679 SPS participants, recruited at the Bishop Lavis Community Health Centre, Cape Town, South Arica. RESULTS: Low or moderate alcohol consumption with or without smoking, nor methamphetamine or marihuana use affected mean MSAFP levels. High MSAFP levels were associated with high alcohol consumption, young age, low body mass index (BMI) (<18 kg/m2) or small mid upper arm circumference (MUAC) (<230mm). High MSAFP levels were associated with stillbirth, preterm birth, abruption and a birth weight z-score of less than -1. CONCLUSION: The study confirms the association between high MSAFP levels and adverse pregnancy outcomes but, although exposure to smoking or drinking is associated with adverse pregnancy outcomes including stillbirth, MSAFP levels were not affected by any of these exposures except for continued high consumption of alcohol. The observed association between higher MSAFP levels and maternal nutritional status (as demonstrated by the lower MUAC and BMI) could explain some of the correlations of poor socioeconomic conditions with higher stillbirth rates effect.

Self-induced vomiting -- risk for oesophageal cancer?

BACKGROUND: Chronic inflammation of the oesophagus is considered a precursor condition for the development of oesophageal cancer. Identification of the causes of chronic oesophageal irritation is therefore relevant in developing preventive measures. Self-induced vomiting is a cultural practice among the black population of South Africa, particularly those living in the Transkei, a region reported to have one of the highest incidences of oesophageal cancer worldwide. METHODS: We retrospectively examined the association between the practice of self-induced vomiting and the development of cytological features of inflammation in 478 self-selected subjects living in Transkei who underwent early screening for oesophageal cancer. Screening involved brush biopsy, cytological investigation and a questionnaire interview. RESULTS: The prevalence of self-induced vomiting was 80.5% and 79.1% in males and females, respectively, and this was stable across all ages. Furthermore, self-induced vomiting was found to be significantly and independently associated with oesophageal chronic inflammation (odds ratio 1.83, 95% confidence interval: 1.13 - 2.96, p = 0.013). CONCLUSION: While the association between the cultural practice of self-induced vomiting and oesophageal cancer has previously been hypothesised, this is the first study to report on an association between this practice and oesophageal chronic inflammation. Further studies that take into account the method used, frequency and duration of vomiting, age of commencement and fasting state of subjects practicing self-induced vomiting coupled with accurate indicators of inflammation are needed to elucidate the role of self-induced vomiting in oesophageal pathogenesis.

Measuring children's self-concept with a Dutch version of the "self-perception profile for children": factorial validity and invariance across a nonclinic and a clinic group.

Harter's (1985) Self-perception Profile for Children (SPPC) is used to investigate whether the pattern and size of relations among the subscales in a clinic group are equivalent to those in a nonclinic group of children, and whether the items are perceived in the same way and with the same degree of accuracy across both groups. The first aspect indicates equivalence of structure, the latter equivalent measurement. Both are aspects of between-group invariance. It is essential to show evidence of these aspects before content-based comparisons are made between these groups. Using restrictive factor analysis, support was found for equivalence of structure. Equivalence of measurement was partially found. The items were perceived in the same way, but not with the same degree of accuracy. The conclusion is that the SPPC has sufficient between-group invariance to be used in studies with children in a clinic group.

Linkage study of the low-density lipoprotein-receptor gene and cholesterol levels in an Afrikaner family. Quantitative genetics and identification of a minor founder effect.

Overlap of clinical and biochemical characteristics between hypercholesterolaemia in members of the general population and familial hypercholesterolaemic (FH) individuals may lead to misdiagnosis. Quantitative analysis of family data may circumvent this problem. A way of looking for an association between plasma cholesterol levels and restriction fragment length polymorphism markers (RFLP) on the low-density lipoprotein (LDL) receptor gene by using reference cholesterol distributions was explored. Linkage, with a logarithm of the odds (LOD) score of 6.8 at theta 0, was detected between cholesterol levels and the LDL receptor in an extended Afrikaner family. Two RFLP-haplotypes, one previously found in a majority of Afrikaner FH homozygotes, and a second, Stu I-, BstE II+, Pvu II+, Nco I+, were associated with high cholesterol levels in this pedigree.