Selecting a birth weight standard for an indigenous population in a LMIC: A prospective comparative study.

OBJECTIVES: The aim of the present study was to compare birth weight (BW) distribution and proportion of BWs below or above specified percentiles in low-risk singleton pregnancies in healthy South African (SA) women of mixed ancestry with expected values according to four BW references and to determine the physiological factors affecting BW. METHODS: This was an ancillary study of a prospective multinational cohort study, involving 7060 women recruited between August 2007 and January 2015 in two townships of Cape Town, characterized by low socioeconomic status, and high levels of drinking and smoking. Detailed information about maternal and pregnancy characteristics, including harmful exposures, was gathered prospectively, allowing us to select healthy women with uncomplicated pregnancies without any known harmful exposures. In this cohort we compared the median BW and the proportion of BWs P90, 95 and 97 according to four reference standards (INTERGROWTH-21st, customized according to the method described by Mickolajczyk, Fetal Medicine Foundation and revised Fenton reference) with expected values. Appropriate parametric and nonparametric tests were used, and sensitivity analysis was performed for infant sex, first trimester bookings and women of normal body mass index (BMI). Multiple regression was used to explore effects of confounders. Written consent and ethics approval was obtained. RESULTS: The cohort included 739 infants. The INTERGROWTH-21st standard was closest for the actual BW-distribution and categories. Below-expected BW was associated with boys, younger, shorter, leaner women, lower parity and gravidity. Actual BW was significantly influenced by maternal weight, BMI, parity and gestational age. CONCLUSION: Of the four references assessed in this study, the INTERGROWTH-21st standard was closest for the actual BW distribution. Maternal variables significantly influence BW.

Association of Placental Histology with the Pulsatility Index of Fetal and Uteroplacental Vessels during Pregnancy and with Birthweight Z-Score.

Aims: To compare macro- and microscopic features of the placenta with the pulsatility index (PI) of the uterine (UtA), umbilical (UA) and middle cerebral arteries at 20-24- and 34-38-weeks' gestation, and with birthweight z-scores (BWZS). Methods: Recruitment for the Safe Passage Study, which investigated the association of alcohol and tobacco use with stillbirth and sudden infant death syndrome, occurred from August 2007 to January 2015 at community clinics in Cape Town, South Africa. The population represents a predominantly homogenous population of pregnant women from a low socioeconomic residential area. This study is a further analysis of the data of the Safe Passage Study. It consists of 1205 singleton pregnancies for which placental histology was available, of whom 1035 had a known BWZS and 1022 and 979 had fetoplacental Doppler examinations performed at Tygerberg Academic Hospital at 20-24 and 34-38 weeks respectively. Features of the placenta were assessed according to international norms. Results: Significantly higher ORs for the presence of individual and combined features of maternal vascular malperfusion (MVM) were found with lower BWZS and higher UtA PI values, more consistently than with higher UA PI values. Strongest associations were for a small placenta for gestational age (UtA OR 4.86 at 20-24 and 5.92 at 34-38 weeks; UA OR 5.33 at 20-24 and 27.01 at 34-38 weeks; low BWZS OR 0.31), for accelerated maturation (UtA OR 11.68 at 20-24 weeks and 18.46 at 34-38 weeks; low BWZS 0.61), for macroscopic infarction (UtA OR 6.08 at 20-24 weeks; UA OR 17.02 at 34-38 weeks; low BWZS OR 0.62) and for microscopic infarction (UtA OR 6.84 at 20-24 and 10.9 at 34-38 weeks; low BWZS OR 0.62). Conclusion: There is considerable variability in the associations between individual features of MVM and increased UtA or UA PI and low BWZS. Although all MVM features currently carry equal weight in defining the condition of MVM, our data suggest that some should carry more weight than others. Macroscopic examination of the placenta may be helpful in identifying placental insufficiency as a small placenta for gestational age and macroscopic infarction were the features most strongly associated with outcomes.

Reference standards for facial measurements in early third trimester South African fetuses, and the effect of maternal and fetal characteristics.

Fetal alcohol spectrum disorder (FASD) is a major problem worldwide and dysmorphic facial features may be a prenatal biomarker for FASD. Deviations from normal facial development cannot be explored before establishing the normal variation in a specific population, since ethnic differences may exist.Objectives: Main objective: to establish reference standards for 23 facial measurements on 3D ultrasound volumes obtained between days 196 and 224 of gestation in healthy unexposed South African fetuses from an area with historically high alcohol consumption prevalence and a population group with no existing normative values. Secondary objective: to assess the confounding effect of maternal and fetal characteristics.Design: This study involves 97 women (including 43 smokers) who had been enrolled in the Safe Passage Study (SPS), a large prospective multinational cohort study assessing the effects of prenatal alcohol exposure. They had adequate 3 D ultrasound volumes of the fetal face acquired at 28+0-31+6 weeks in singleton pregnancies without comorbidities, congenital abnormalities or exposure to alcohol, marijuana, or methamphetamines from 4 weeks before conception.Participants, materials, setting, methods: The participants were recruited from two residential areas of low socioeconomic status in Cape Town. Meticulous information was collected on maternal and pregnancy characteristics, including alcohol use at different time points. Gestational age (GA) was based on ultrasound biometry before 24 weeks, and 3D ultrasound volumes were acquired trans-abdominally from a sagittal and axial plane of the fetal face. Volumes were independently assessed offline by two observers and the image with the best landmark definition was used for 23 facial measurements, representing features previously described in children with FASD. The relation to the exact GA was assessed by regression analysis, the expected mean value and standard error of the estimate (SEE) was determined to transform all raw measurements into z-scores, and the effect of possible confounders on z-scores was assessed by ANOVA.Results: Ten variables changed significantly with advancing GA (extraocular diameter, anteroposterior, medio-lateral and supero-inferior ocular diameter, ocular volume, interlens distance, prenasal thickness, nasal bone length, nose length and nose protrusion) and thirteen did not (interocular distance; interocular: extraocular diameter ratio, prenasal thickness: nasal bone length ratio, pronasal-subnasal distance, subnasal-mouth distance, philtrum length, upper vermillion thickness, nose-philtrum angle, maxillary angle, facial height, facial protrusion, frontomaxillary facial angle and maxilla-nasion-mandible angle). Reference values (expected mean and SEE) for the 23 measurements were established for each day.The z-scores of all facial measurements were not independently affected by maternal age, parity, gravidity, smoking or body mass index, but infant sex and birthweight z-score significantly influenced several z-scores (infant sex for extraocular, medio-lateral, and supero-inferior ocular diameter, ocular volume, prenasal thickness and nose protrusion; birthweight z-score for extraocular diameter, interocular and interlens distance, nose protrusion and maxillary angle).Limitations: GA was not always confirmed by first trimester ultrasound and some measurements could not be obtained in all cases due to suboptimal image quality. The cohort included few heavy smokers so an effect of heavy or continued smoking cannot be ruled out, and the effect of ethnicity was not assessed.Conclusions: These are the first local reference standards for fetal facial measurements and, to our knowledge, the first reference standards for the supero-inferior ocular diameter, face protrusion, upper vermillion thickness, maxillary angle, and nose-philtrum angle. They were broadly in keeping with published references, with small discrepancies explained by minor differences in technique. Even in this narrow GA window, the distribution of many variables changed over time and normal variation was significantly influenced by fetal sex and birthweight z-score. The possible confounding effect of these factors needs to be considered when assessing the impact of harmful exposures like alcohol on facial development.

Maternal childhood trauma, postpartum depression, and infant outcomes: Avoidant affective processing as a potential mechanism.

BACKGROUND: Women who have experienced childhood trauma may be at risk for postpartum depression, increasing the likelihood of negative outcomes among their children. Predictive pathways from maternal childhood trauma to child outcomes, as mediated by postpartum depression, require investigation. METHODS: A longitudinal sample of South African women (N=150) was followed through pregnancy and postpartum. Measures included maternal trauma history reported during pregnancy; postpartum depression through six months; and maternal-infant bonding, infant development, and infant physical growth at one year. Structural equation models tested postpartum depression as a mediator between maternal experiences of childhood trauma and children's outcomes. A subset of women (N=33) also participated in a lab-based emotional Stroop paradigm, and their responses to fearful stimuli at six weeks were explored as a potential mechanism linking maternal childhood trauma, postpartum depression, and child outcomes. RESULTS: Women with childhood trauma experienced greater depressive symptoms through six months postpartum, which then predicted negative child outcomes at one year. Mediating effects of postpartum depression were significant, and persisted for maternal-infant bonding and infant growth after controlling for covariates and antenatal distress. Maternal avoidance of fearful stimuli emerged as a potential affective mechanism. LIMITATIONS: Limitations included modest sample size, self-report measures, and unmeasured potential confounders. CONCLUSIONS: Findings suggest a mediating role of postpartum depression in the intergenerational transmission of negative outcomes. Perinatal interventions that address maternal trauma histories and depression, as well as underlying affective mechanisms, may help interrupt cycles of disadvantage, particularly in high-trauma settings such as South Africa.

Placental insufficiency among high-risk pregnancies with a normal umbilical artery resistance index after 32weeks.

OBJECTIVE: To determine the incidence of abnormal multi-vessel Doppler values among advanced pregnancies at risk of suboptimal placentation but with a normal umbilical artery resistance index (RI), and to assess whether clinical and ultrasonography findings can identify them. METHODS: In a prospective cross-sectional study at Tygerberg Hospital, South Africa, women with high-risk pregnancies but normal umbilical artery RI after 32weeks underwent ultrasonography (fetal biometry, liquor, and placenta maturation) and Doppler assessment (uterine, umbilical, and middle cerebral arteries) between February 11 and October 21, 2013. Study data were compared among four groups: fetuses with normal uterofetoplacental Doppler values and those with any abnormal pulsatility index, each subdivided into small for gestational age (SGA) and appropriate for gestational age (AGA) by estimated fetal weight. RESULTS: Of 210 participants, 72 (36.2%) had abnormal Doppler results, and 60 (28.6%) fetuses were SGA (38 [63.3%] with abnormal Doppler results). Clinical characteristics did not differ between groups with normal or abnormal Doppler values; however, among normal Doppler results, SGA pregnancies demonstrated poorer fundal growth (P=0.006). Significant associations existed between abnormal Doppler results and asymmetric growth, inappropriately advanced placental maturation, and reduced liquor volume (all P≤0.04), but with very low sensitivities (3.9%, 4.8%, and 14.5%, respectively). CONCLUSION: Maternal characteristics and imaging variables did not reliably identify more than one-third of pregnancies with evidence of suboptimal placentation.

A comparison of pregnancy dating methods commonly used in South Africa: a prospective study.

BACKGROUND: Pregnancy dating in the South African public healthcare setting is mainly based on clinical assessment. However, the accuracy of this approach is unknown. AIM: To compare the accuracy of different pregnancy dating methods. METHODS: We performed a prospective comparison of 2 ultrasound policies involving consecutive low-risk women in a midwife clinic in the Metro East region, Cape Town, Western Cape. Information on the last menstrual period (LMP), the 1st symphysis-to-fundal height measurement (FH) and average gestation by ultrasonographic (US) fetal biometry was recorded. Five dating methods: LMP, FH, US and their combinations, were assessed against the actual day of delivery (ADD). The main outcome measures were: (i) the days between the ADD and estimated date of delivery in pregnancies where spontaneous labour occurred and the baby had a normal birth weight; (ii) the incidence of gestational age-related outcomes; and (iii) the influence of clinical variables on dating discrepancies. RESULTS: A total of 1 342 pregnancies were analysed. The accuracy of dating was similar for certain and uncertain LMP. FH was less accurate with increasing obesity. US-based dating was most accurate (for 85% of predictions within 14 days) and similarly accurate at 20 - 24 weeks and at >24 weeks. US reduced the number of assumed pre-and post-term deliveries and, in addition, was better at detecting small-for-gestational age infants (p<0.001). CONCLUSION: Pregnancy dating by US, including those in more advanced pregnancies than currently permitted, is recommended since all non-ultrasound-based estimations of gestational age were considerably less accurate.

Risk factors for substance use in pregnant women in South Africa.

OBJECTIVES: To study the prevalence of alcohol and substance use in a South African antenatal population and its correlates with socio-demographic factors, depression and perceived stress. METHODS: A prospective self-report study on all women presenting for their first antenatal visit who consented to the study at a midwife obstetric unit (MOU) in the East Metropole district, Cape Town, using the Alcohol Use Disorders Identification Test (AUDIT), Drug Use Disorders Identification Test (DUDIT), Edinburgh Depression Scale (EDS) and Perceived Stress Scale (PSS). Statistical analyses using the chi-square test, separate one-way analyses of variance (ANOVA) and logistic regression analyses were performed as appropriate. Outcome measures were depression, alcohol use and substance use. RESULTS: The questionnaire was completed by 323 women. During pregnancy 36.8% of women smoked, 20.2% used alcohol and 4% used substances. Using EDS cut-off scores of 12 and 15, respectively, 48.9% and 33.6% of the sample had scores consistent with major depression. An EDS cut-off score of 12 was significantly associated with both alcohol use (25.9% v. 15.2%, p=0.019) and risky drinking (76.9% v. 36.8%, p=0.04), while an EDS cut-off score of 15 was significantly associated with substance use (8.2% v. 1.4%, p=0.004) as well as alcohol dependence (23.1% v. 3.1%). CONCLUSIONS: We found high rates of both alcohol abuse and antenatal depression, and a significant association between depression, substance use and alcohol abuse; EDS scores greater than 12 could be used to identify women at risk of alcohol dependence and/or substance abuse.

Which is the most accurate formula to estimate fetal weight in women with severe preterm preeclampsia?

OBJECTIVE: To identify the most accurate formula to estimate fetal weight (EFW) from ultrasound parameters in severe preterm preeclampsia. METHODS: In a prospective study, serial ultrasound assessments were performed in 123 women with severe preterm preeclampsia. The EFW, calculated for 111 live born, normal, singleton fetuses within 7 days of delivery using 38 published formulae, was compared to the actual birth weight (ABW). Accuracy was assessed by correlations, mean (absolute and signed) (%) errors, % correct predictions within 5-20% of ABW and limits of agreement. RESULTS: Accuracy was highly variable. Most formulae systematically overestimated ABW. Five Hadlock formulae utilizing three or four variables and Woo 3 formula had the highest accuracy and did not differ significantly (mean absolute % errors 6.8-7.2%, SDs 5.3-5.8%, > 75% of estimations within 10% of ABW and 95% limits of agreement between -18/20% and +14/15%). They were not negatively affected by clinical variables but had some inconsistency in bias over the ABW range. All other formulae, including those targeted for small, preterm or growth restricted fetuses, were inferior and/or affected by multiple clinical variables. CONCLUSION: In this GA window, Hadlock formulae using three or four variables or Woo 3 formula can be recommended.

Association between antenatal distress and uterine artery pulsatility index.

Although studies have found associations between maternal distress/anxiety and alterations in blood flow, data across different trimesters are inconsistent. We, therefore, sought to determine the association between measures of distress and uterine blood flow in all three trimesters. Healthy women with low-risk singleton pregnancies were recruited from antenatal clinics. Women were assessed at 13-14 weeks (T1), 21-22 weeks (T2), and 32-33 weeks (T3) of gestation with measures of distress and anxiety (the K10, Perceived Stress Scale, and the State Subscale of the Spielberger State-Trait Anxiety Inventory [STAI]) and with uterine Doppler flow velocity studies. The Trait Subscale of the STAI was done either at T1 or T2. Thirty women were seen at T1, 79 women were seen at T2, and 59 women were seen at T3. No significant correlations were found between measures of distress and anxiety and umbilical artery pulsatility index (PI) or middle cerebral artery PI at any time-point. Small positive correlations between trait anxiety and uterine artery PI were found, but these were not significant after adjustment for alcohol and nicotine use (any use as well as problem drinking/nicotine dependence). At T3 but not T1 or T2, women scoring above 20 on the K10 (a standardized cutoff for the presence of axis I psychiatric disorders) had higher uterine artery PI than those scoring below 20.This was significant after adjusting for alcohol and nicotine use, as well as when nicotine dependence was considered. This work highlights the complexities of the relationship between increased measures of distress and anxiety and changes in the placental circulation. Further work in this area is needed to explore the underlying mechanisms which account for this relationship and to delineate fully the extent to which the relationship is determined by the presence of psychiatric and substance use disorders.

Centile charts of cervical length between 18 and 32 weeks of gestation.

OBJECTIVE: To establish a centile chart of cervical length between 18 and 32 weeks of gestation in a low-risk population of women. METHODS: A prospective longitudinal cohort study of women with a low risk, singleton pregnancy using public healthcare facilities in Cape Town, South Africa. Transvaginal measurement of cervical length was performed between 16 and 32 weeks of gestation and used to construct centile charts. The distribution of cervical length was determined for gestational ages and was used to establish estimates of longitudinal percentiles. Centile charts were constructed for nulliparous and multiparous women together and separately. RESULTS: Centile estimation was based on data from 344 women. Percentiles showed progressive cervical shortening with increasing gestational age. Averaged over the entire follow-up period, mean cervical length was 1.5 mm shorter in nulliparous women compared with multiparous women (95% CI, 0.4-2.6). CONCLUSIONS: Establishment of longitudinal reference values of cervical length in a low-risk population will contribute toward a better understanding of cervical length in women at risk for preterm labor.

Prenatal diagnosis of chromosomal abnormalities in a resource-poor setting.

OBJECTIVE: To compare the efficacy and efficiency of systematic, ultrasound-based risk adjustment using a published algorithm with that of a maternal age cutoff of 37 years for the prenatal detection of chromosomal abnormalities (especially autosomal trisomies). METHODS: These approaches were compared in a retrospective study of 136 chromosomal abnormalities confirmed by karyotyping prenatally (n=46) or postnatally (n=90). There were 114 autosomal trisomies. RESULTS: Maternal age was known for 103 fetuses with confirmed abnormalities. The ultrasound-based risk adjustment approach was more sensitive for autosomal trisomy (93.9% vs 44.1%), and karyotyping for younger women with abnormalities on ultrasound was more effective than routine karyotyping in older women (1 trisomy detected in 13.5 vs 42.8 samples, P<0.001). A lack of screening was the main reason for the postnatal diagnosis. CONCLUSION: Ultrasound-based risk adjustment was the more effective approach.

Impaired vascular reactivity in pregnant women with insulin-dependent diabetes mellitus.

OBJECTIVE: The purpose of this study was to investigate the vascular function of pregnant women with insulin-dependent diabetes mellitus, using a noninvasive method. STUDY DESIGN: This was a cross-sectional study that examined vascular function, which was assessed by flow-mediated dilatation of the brachial artery, in 37 pregnant women with insulin-dependent diabetes mellitus and in 37 healthy pregnant women at 20 weeks of gestation. The control of diabetes was also assessed by the measurement of glycosylated hemoglobin. Data were analyzed by 2-sided unpaired t test and multivariate regression analysis. RESULTS: In the pregnant women with insulin-dependent diabetes mellitus, flow-mediated dilatation of the brachial artery was significantly lower than in healthy pregnant women (6.43% +/- 3.66% vs 9.43% +/- 3.69%, respectively; P =.0008). This difference was apparent even after an adjustment was made for blood vessel diameter, which was different between the 2 populations (P =.01). Flow-mediated dilatation in diabetic women was significantly correlated with the duration of diabetes (P =.01) but not with the levels of glycosylated hemoglobin. CONCLUSION: Maternal insulin-dependent diabetes mellitus is associated with an impaired vasodilatory response to a blood flow stimulus. This vascular dysfunction is associated with the duration of the diabetes.