Correction of Systematic Bias in Ultrasound Dating in Studies of Small-for-Gestational-Age Birth: An Example From the Iowa Health in Pregnancy Study

The authors examined whether early ultrasound dating (≤20 weeks) of gestational age (GA) in small-for-gestational-age (SGA) fetuses may underestimate gestational duration and therefore the incidence of SGA birth. Within a population-based case-control study (May 2002-June 2005) of Iowa SGA births and preterm deliveries identified from birth records (n = 2,709), the authors illustrate a novel methodological approach with which to assess and correct for systematic underestimation of GA by early ultrasound in women with suspected SGA fetuses. After restricting the analysis to subjects with first-trimester prenatal care, a nonmissing date of the last menstrual period (LMP), and early ultrasound (n = 1,135), SGA subjects' ultrasound GA was 5.5 days less than their LMP GA, on average. Multivariable linear regression was conducted to determine the extent to which ultrasound GA predicted LMP dating and to correct for systematic misclassification that results after applying standard guidelines to adjudicate differences in these measures. In the unadjusted model, SGA subjects required a correction of +1.5 weeks to the ultrasound estimate. With adjustment for maternal age, smoking, and first-trimester vaginal bleeding, standard guidelines for adjudicating differences in ultrasound and LMP dating underestimated SGA birth by 12.9% and overestimated preterm delivery by 8.7%. This methodological approach can be applied by researchers using different study populations in similar research contexts.     

Variation between last-menstrual-period and clinical estimates of gestational age in vital records

An accurate assessment of gestational age is vital to population-based research and surveillance in maternal and infant health. However, the quality of gestational age measurements derived from birth certificates has been in question. Using the 2002 US public-use natality file, the authors examined the agreement between estimates of gestational age based on the last menstrual period (LMP) and clinical estimates in vital records across durations of gestation and US states and explored reasons for disagreement. Agreement between the LMP and the clinical estimate of gestational age varied substantially across gestations and among states. Preterm births were more likely than term births to have disagreement between the two estimates. Maternal age, maternal education, initiation of prenatal care, order of livebirth, and use of ultrasound had significant independent effects on the disagreement between the two measures, regardless of gestational age, but these factors made little difference in the magnitude of gestational age group differences. Information available on birth certificates was not sufficient to understand this disparity. The lowest agreement between the LMP and the clinical estimate was observed among preterm infants born at 28-36 weeks' gestation, who accounted for more than 90% of total preterm births. This finding deserves particular attention and further investigation.     

The research implications of the selection of a gestational age estimation method

There are three primary methods of gestational age estimation: dating based on last menstrual period (LMP), ultrasound-based dating and neonatal estimates. We review the strengths and limitations of each method as well as their implications for research. Dating based on LMP is a simple, low-cost method of estimating gestational age. Limitations associated with the use of menstrual-based dating include reporting problems such as uncertainty regarding the LMP date, possibly due to bleeding not associated with menses, as well as concerns about the incidence of delayed ovulation, which can result in invalid estimates of gestation, even for women with certain LMP dates. Given that most women in the US have at least one ultrasound during pregnancy, it is becoming increasingly common for clinicians to verify menstrual dates using early ultrasound. To calculate gestational age with the use of ultrasound, fetal measurements are compared with a gestational age-specific reference. The primary limitation of this method is the fact that the gestational age estimates of symmetrically large or small fetuses will be biased. Further, given that ultrasound references were developed using pregnancies that were dated according to reliable LMP dates, they are potentially biased in the same direction as dates calculated according to LMP. Neonatal estimates of gestational age have been shown to be the least precise dating method. To highlight the research implications of the choice of a gestational dating method, we used data from the Routine Antenatal Diagnostic Imaging with Ultrasound Study to identify risk factors for post-term delivery. Risk factors for post-term delivery are shown to vary according to the choice of a gestational dating method, suggesting that some findings are an artefact of the choice of a method rather than evidence of causality.     

The accuracy of using last menstrual period to determine gestational age for first trimester medication abortion: a systematic review

Objective

We sought to evaluate the accuracy of assessing gestational age (GA) prior to first trimester medication abortion using last menstrual period (LMP) compared to ultrasound (U/S).

Study Design

We searched Medline, Embase and Cochrane databases through October 2013 for peer-reviewed articles comparing LMP to U/S for GA dating in abortion care. Two teams of investigators independently evaluated data using standard abstraction forms. The US Preventive Services Task Force and Quality Assessment of Diagnostic Accuracy Studies guidelines were used to assess quality.

Results

Of 318 articles identified, 5 met inclusion criteria. Three studies reported that 2.5–11.8% of women were eligible for medication abortion by LMP and ineligible by U/S. The number of women who underestimated GA using LMP compared to U/S ranged from 1.8 to 14.8%, with lower rates found when the sample was limited to a GA < 63 days. Most women (90.5–99.1%) knew their LMP, 70.8–90.5% with certainty.

Conclusion

Our results support that LMP can be used to assess GA prior to medication abortion at GA < 63 days. Further research looking at patient outcomes and identifying women eligible for medication abortion by LMP but ineligible by U/S is needed to confirm the safety and effectiveness of providing medication abortion using LMP alone to determine GA.     

Trimester of Maternal Gestational Weight Gain and Offspring Body Weight at Birth and Age Five

To investigate associations of trimester-specific GWG with fetal birth size and BMI at age 5?years. We examined 3,015 singleton births to women without pregnancy complications from the Child Health and Development Studies prospective cohort with measured weights during pregnancy. We used multivariable regression to examine the associations between total and trimester gestational weight gain (GWG) and birth weight for gestational age and child BMI outcomes, adjusting for maternal age, race/ethnicity, education, marital status, parity, pre-pregnancy body mass index (BMI), and smoking; paternal overweight, gestational age, and infant sex. We explored differences in associations by maternal BMI and infant sex. GWG in all trimesters was significantly and independently associated with birth weight with associations stronger, though not significantly, in the second trimester. First trimester GWG was associated with child BMI outcomes (OR for child overweight?=?1.05; 95% CI?=?1.02, 1.09). Each kg of first trimester GWG was significantly associated with increased child BMI z-score in women of low (???=?0.099; 95% CI?=?0.034, 0.163) and normal (???=?0.028; 95% CI?=?0.012, 0.044), but not high pre-pregnancy BMI. GWG in all trimesters was associated with birth weight; only first trimester GWG was associated with child BMI. If replicated, this information could help specify recommendations for maternal GWG and elucidate mechanisms connecting GWG to child BMI.     

Timing of Incarceration During Pregnancy and Birth Outcomes: Exploring Racial Differences

Objectives To examine whether there are racial differences in the relation between the timing of incarceration during pregnancy and birth outcomes among incarcerated pregnant women. Methods We examined the medical records associated with 360 infants born to pregnant inmates in Texas state prisons between January 1, 2002 and December 31, 2004. Weighted linear regression was used, within racial strata, to model gestational age at delivery, and infant birth weight, respectively, as functions of gestational age at maternal admission to prison. Models were adjusted for maternal age; gravidity; educational attainment; history of tobacco, substance, and alcohol use and the presence of any maternal chronic disease. Results Among Whites there was a 360.8 g lower mean birth weight for infants born to women incarcerated during weeks 14–20 relative to infants born to women incarcerated during weeks 1–13 (p < 0.10). Among Blacks and Hispanics, incarceration after the first trimester was not associated with a significant decrease in infant birth weight relative to incarceration during the first trimester. White women entering prison during the first trimester delivered infants at higher gestational ages than White women entering in the second trimester but the opposite was the case for Hispanics. Conclusions The association between the quantity of exposure to prison during pregnancy and birth outcomes appears to be different for Blacks, Whites, and Hispanic women. Future studies of the effect of incarceration on pregnancy outcomes should attempt to uncover potential racial differences in trends by obtaining racially stratified results or by assessing interaction with race.     

Maternal protein intake is not associated with infant blood pressure

BACKGROUND: Animal data show that low protein intake in pregnancy programs higher offspring blood pressure, but similar data in humans are limited. We examined the associations of first and second trimester maternal protein intake with offspring blood pressure (BP) at the age of six months. METHODS: In a prospective US cohort study, called Project Viva, pregnant women completed validated semi-quantitative food-frequency questionnaires (FFQ) to measure gestational protein intake. Among 947 mother-offspring pairs with first trimester dietary data and 910 pairs with second trimester data, we measured systolic blood pressure (SBP) up to five times with an automated device in the offspring at the age of six months. Controlling for blood pressure measurement conditions, maternal and infant characteristics, we examined the effect of energy-adjusted maternal protein intake on infant SBP using multivariable mixed effects models. RESULTS: Mean daily second trimester maternal protein intake was 17.6% of energy (mean 2111 kcal/day). First trimester nutrient intakes were similar. Mean SBP at age 6 months was 90.0 mm Hg (SD 12.9). Consistent with prior reports, adjusted SBP was 1.94 mm Hg lower [95% confidence interval (CI) -3.45 to -0.42] for each kg increase in birth weight. However, we did not find an association between maternal protein intake and infant SBP. After adjusting for covariates, the effect estimates were 0.14 mm Hg (95% CI 20.12 to 20.40) for a 1% increase in energy from protein during the second trimester, and 20.01 mm Hg (95% CI 20.24 to -0.23) for a 1% increase in energy from protein in the first trimester. CONCLUSIONS: Variation in maternal total protein intake during pregnancy does not appear to program offspring blood pressure.     

Predicting large fetuses at birth: do multiple ultrasound examinations and longitudinal statistical modelling improve prediction?

Zhang J, Kim S, Grewal J, Albert PS. Predicting large fetuses at birth: do multiple ultrasound examinations and longitudinal statistical modelling improve prediction? Paediatric and Perinatal Epidemiology 2012; 26 : 199–207. Predicting large fetuses at birth has long been a challenge in obstetric practice. We examined whether ultrasound examinations at multiple times during pregnancy improve the accuracy of prediction using repeated, longitudinal statistical modelling, and whether adding maternal characteristics improves the accuracy of prediction. We used data from a previous study conducted in Norway and Sweden from 1986 to 1989 in which each pregnant woman had four ultrasound examinations at around 17, 25, 33 and 37 weeks of gestation. At birth, infant size was classified as large‐for‐gestational age (LGA, >90th centile) and macrosomia (>4000 g) or not. We used a longitudinal random effects model with quadratic fixed and random effects to predict term LGA and macrosomia at birth. Receiver–operator curves and mean‐squared error were used to measure accuracy of the prediction. Ultrasound examination around 37 weeks had the best accuracy in predicting LGA and macrosomia at birth. Adding multiple ultrasound examinations at earlier gestations did not improve the accuracy. Adjusting for maternal characteristics had limited impact on the accuracy of prediction. Thus, a single ultrasound examination at late gestation close to birth is the simplest method currently available to predict LGA and macrosomia.     

The use of covariates to identify records with implausible gestational ages using the birthweight distribution

Parker JD, Liao D, Schenker N, Branum A. The use of covariates to identify records with implausible gestational ages using the birthweight distribution. Paediatric and Perinatal Epidemiology 2010. The objective of this study was to evaluate the usefulness of covariates in identifying birth records with implausible values of gestational age. Birthweight distributions for births with early reported gestational ages are markedly bimodal, suggesting a mixture of two distributions. Most births form a normal‐shaped left‐hand (primary) distribution and a smaller number form the right‐hand (secondary) distribution. The births in the secondary distribution are thought to have gestational age mistakenly reported. Prior work has found that births in the secondary distribution are at higher risk of poor outcomes than those in the primary distribution. Using 2002 US Natality data for gestational ages 26–35 weeks, we fit normal mixture models to birthweight with and without covariates (maternal race, education, parity, age, region of the country, prenatal care initiation) by reported gestational age. Additional models were stratified by infant sex. This approach allowed for the relationship between the covariates and birthweight to differ between the components. Mixture models fit reasonably well for reported gestational ages <33 weeks, but not for later weeks. Counter to the hypothesis, results were similar for models with and without covariates or stratification or both, although stratified models without covariates predicted slightly more girls and slightly fewer boys in the secondary distribution than did the corresponding unstratified models. For reported gestational ages <33 weeks, predictions from the four sets of models were highly correlated and predictions were similar for subgroups defined by the clinical estimates of gestational age and other covariates. For births with reported gestational ages of 29 or more weeks, the proportion in the secondary distribution exceeded 30%, although this varied by maternal characteristics. The use of covariates and stratification complicated model fitting without materially improving identification of implausible gestational age values, supporting inferences from prior studies using data ‘cleaned’ without consideration of maternal or infant characteristics.     

United States vital statistics and the measurement of gestational age

Estimates of the gestational age of the newborn based on US Birth Certificate data are extensively used to monitor trends in infant and maternal health and to improve our understanding of adverse pregnancy outcome. Two measures of gestational age, the 'date of the last normal menses' (LMP) and the 'clinical estimate of gestation' (CE), have been available from birth certificate data since 1989. Reporting irregularities with the LMP-based measure are well-documented, and important questions remain regarding the derivation of the CE. Changes in perinatal medicine and in vital statistics reporting in recent years may have importantly altered gestational age data based on vital statistics. This study describes how gestational age measures are collected and edited in US national vital statistics, and examines changes in the reporting of these measures by race and Hispanic origin between 1990 and 2002. Data are drawn from the National Center for Health Statistics' restricted use US birth files for 1990–2002. Bivariable statistics are used.
The percentage of records with missing LMP dates declined markedly over the study period, overall, and for each racial/Hispanic origin group studied. A marked shift in the distribution of the CE of gestational age was also observed, suggesting changes both in the true distribution of age at birth, and in the derivation of this measure. Agreement between the LMP-based and CE estimates increased over the study period, especially among preterm births. However, a high proportion of LMP dates continue to be missing or invalid and the derivation of the CE is still uncertain. In sum, although the reporting of gestational age measures in vital statistics appears to have improved between 1990 and 2002, substantial concerns with both the LMP-based and the CE persist. Efforts to identify approaches to further improve upon the quality of these data are needed.     

产前抑郁对新生儿出生体质量和分娩孕周的影响

目的探讨产前抑郁与胎儿出生体质量和分娩孕周的相关性。方法选取2011年8月-2018年5月在舟山市妇幼保健院产检的1 616例孕妇为研究对象,采用自编问卷采集研究对象一般社会人口学信息、器质性疾病、精神疾病、创伤史及分娩史,采用抑郁自评量表(SDS)评价抑郁状态,采用焦虑自评量表(SAS)评价焦虑状态,并从舟山市妇幼保健院电子医疗系统中提取分娩的相关信息,采用多元线性回归分析产前抑郁与胎儿出生体质量和分娩孕周的相关性。结果孕期无抑郁组脑力劳动者、高孕次人数、出现早孕反应及孕期存在焦虑的比例均少于孕期有抑郁组,差异均有统计学意义(均P<0. 001);无抑郁组平均文化水平高于有抑郁组,差异有统计学意义(P<0. 001)。多元线性回归分析结果显示,产前抑郁与孕妇分娩孕周无关;孕早期中重度抑郁能降低胎儿出生体质量(β=-69. 76,P=0. 039 1),各怀孕阶段中至少1期(β=-59. 05,P=0. 005 1)、至少2期(β=-61. 49,P=0. 027 1)出现抑郁均能降低胎儿出生体质量,至少1期出现中重度抑郁(β=-88. 03,P=0. 004 5)对降低胎儿出生体质量的效应更为显著。结论产前抑郁与胎儿出生体质量呈负相关关系,但与出生孕周无关,因此要加强孕妇的心理健康管理,维护母婴健康。     

10407名单胎活产儿SGA发生率及其影响因素的队列研究

目的:了解安徽省8地市小于胎龄儿(SGA)发生情况并分析其影响因素。方法:选择安徽省8地市妇幼保健部门首次保健服务的孕妇为研究对象,填写《孕产期母婴健康记录表》,收集母亲的社会人口统计学特征和孕前6个月及孕早期环境暴露因素,同时于孕晚期收集孕期妊娠期高血压等妊娠合并症及并发症的发生情况,记录单胎活产儿出生信息,运用χ2检验和多因素Logistics回归模型分析人口统计学特征与环境暴露对SGA的影响。结果:SGA发生率为3.4%(357/10 407),将SGA按重量指数分型,匀称型SGA占55.2%(197/357),非匀称型SGA占43.4%(155/357);将SGA按身长/头围分型,为匀称型SGA占73.7%(263/357),非匀称型SGA占4.2%(15/357)。多因素Logistic回归模型结果显示,孕妇为城市户口、孕早期发生妊娠呕吐但未做医疗处理、孕期头3个月服用微量元素坚持1个月以上是SGA发生的保护因素,OR值分别为0.71(95%CI:0.57～0.89)、0.79(95%CI:0.63～0.99)、0.30(95%CI:0.11～0.81);胎儿性别为女、孕前BMI<18.5、发生妊娠呕吐并去医院就诊为SGA的危险因素,OR值分别为1.83(95%CI:1.47～2.29)、1.46(95%CI:1.16～1.85)、1.72(95%CI:1.12～2.65)。结论:孕妇孕前BMI较低及妊娠呕吐等会影响SGA的发生,加强孕前和孕期保健,应重视妊娠呕吐的发生,发生时应及时就诊以减少SGA的发生。     

Last menstrual period provides the best estimate of gestation length for women in rural Guatemala

The accurate estimation of gestational age in field studies in rural areas of developing countries continues to present difficulties for researchers. Our objective was to determine the best method for gestational age estimation in rural Guatemala. Women of childbearing age from four communities in rural Guatemala were invited to participate in a longitudinal study. Gestational age at birth was determined by an early second trimester measure of biparietal diameter, last menstrual period (LMP), the Capurro neonatal examination and symphysis-fundus height (SFH) for 171 women-infant pairs. Regression modelling was used to determine which method provided the best estimate of gestational age using ultrasound as the reference. Gestational age estimated by LMP was within +/-14 days of the ultrasound estimate for 94% of the sample. LMP-estimated gestational age explained 46% of the variance in gestational age estimated by ultrasound whereas the neonatal examination explained only 20%. The results of this study suggest that, when trained field personnel assist women to recall their date of LMP, this date provides the best estimate of gestational age. SFH measured during the second trimester may provide a reasonable alternative when LMP is unavailable.     

Trends and differentials in higher-birthweight infants at 28–31 weeks of gestation, by race and Hispanic origin, United States, 1990–2002

Birth certificate gestational age data based on the date of the mother's last menstrual period (LMP) are considered problematic. Of particular concern are birthweight distributions for infants reported on the birth certificate as having been delivered at 28–31 weeks' gestation; these distributions have been shown to be distinctly bimodal. The 'second curve' of the birthweight distribution at 28–31 weeks includes implausible birthweight/gestational age combinations and, thus, has been hypothesised to represent erroneous gestational ages due to misidentification of the date of LMP. It has been suggested that such 'misclassification' has declined in recent years and that this change can affect trends in preterm birth rates (<37 weeks' gestation), particularly rates among non-Hispanic black infants. This present study used primarily simple and multivariable analyses to review trends and differentials in birthweight distributions at 28–31 weeks by race and Hispanic origin of the mother. It aggregated data for the years 1990–92 and 2000–02 from the US vital statistics Natality files.
Over the decade, the percentage of births in the second curve declined for all births and for each racial and Hispanic origin group studied. The largest decline was observed for non-Hispanic blacks; the smallest for Hispanic births. Later initiation of prenatal care, younger maternal age, lower educational attainment, higher birth order and vaginal and singleton delivery were positively associated with a larger second curve, suggesting misclassification of gestational age. Declines in the second curve over the study period were suggested to contribute significantly to the observed decrease in overall preterm birth rates for non-Hispanic black births. Further analysis is needed to estimate the influence of reporting error on preterm birth rates by race and Hispanic origin.     

The Japan Environment and Children’s Study (JECS): A Preliminary Report on Selected Characteristics of Approximately 10 000 Pregnant Women Recruited During the First Year of the Study

Background

The Japan Environment and Children’s Study (JECS) is an ongoing nationwide birth cohort study launched in January 2011. In this progress report, we present data collected in the first year to summarize selected maternal and infant characteristics.

Methods

In the 15 Regional Centers located throughout Japan, the expectant mothers were recruited in early pregnancy at obstetric facilities and/or at local government offices issuing pregnancy journals. Self-administered questionnaires were distributed to the women during their first trimester and then again during the second or third trimester to obtain information on demographic factors, physical and mental health, lifestyle, occupation, environmental exposure, dwelling conditions, and socioeconomic status. Information was obtained from medical records in the first trimester and after delivery on medical history, including gravidity and related complications, parity, maternal anthropometry, and infant physical examinations.

Results

We collected data on a total of 9819 expectant mothers (mean age = 31.0 years) who gave birth during 2011. There were 9635 live births. The selected infant characteristics (singleton births, gestational age at birth, sex, birth weight) in the JECS population were similar to those in national survey data on the Japanese general population.

Conclusions

Our final birth data will eventually be used to evaluate the national representativeness of the JECS population. We hope the JECS will provide valuable information on the impact of the environment in which our children live on their health and development.Key words: birth cohort, pregnant women, children, environmental chemicals, Japan     

Assessing the quality of last menstrual period date on California birth records

Birth certificate last menstrual period (LMP) date is widely used to estimate gestational age in the US. While data quality concerns have been raised, no large population-based study has isolated data quality issues by comparing birth record LMP (Birth LMP) with reliable LMP dates from another source. We assessed LMP data quality in 2002 California singleton livebirth records ( n  = 515 381) and in a subset of records with linked prenatally collected LMP from California's statewide Prenatal Expanded Alpha-fetoprotein Screening Program (XAFP) ( n  = 105 936). Missing or incomplete LMP data affected 13% of birth records; 17% of those had complete LMP within XAFP records.
Data quality indicators supported XAFP LMP as more accurate than Birth LMP, with a lower prevalence of digit preference, post-term delivery, out-of-range gestational age estimates and implausible birthweight-for-gestational age. The bimodal birthweight distribution evident at 20–31 weeks' gestation based on Birth LMP was nearly absent with XAFP LMP-based gestational age. Approximately 32% of the second birthweight mode was explained by apparent clerical errors in Birth LMP month. Digit preference errors, particularly day 1, were associated with gestational age overestimation. Preterm delivery rates were higher according to Birth (7.6%) vs. XAFP LMP (7.2%). One-fifth of observed preterm and over half of observed post-term births using Birth LMP were not true cases; 15% of true preterm cases were missed. African American or Hispanic, less educated, and publicly or uninsured women were most likely to be misclassified and have large LMP date discrepancies attributable to clerical or digit preference error. The implementation of a revised birth certificate is an opportunity for targeted training and data entry checks that could substantially improve LMP accuracy on birth records.     

Factors associated with the timing of abortions

The timing of an abortion (often measured as gestational age) can have important effects on the woman's physical health and on the cost of the procedure. To the authors' knowledge, there has been only one national analysis of the factors associated with the gestational age at abortion, but it employed data from over 20 years ago. The state‐specific studies that have explored abortion timing have typically examined the effects of a specific change in abortion regulations. In this study, we employ annual, state‐level data covering the 1991–2014 period that measure the frequency of abortions by gestational age. We regress these measures of abortion utilization on policy, economic, demographic, and health care infrastructure characteristics. The estimates indicate that the introduction of state restrictions on Medicaid funding of abortions is associated with a 13% increase in the rate of abortions after the first trimester. We do not find a statistically significant association between parental involvement laws and the rate or percentage of post‐first‐trimester abortions.     

Preferences for a third‐trimester ultrasound scan in a low‐risk obstetric population: a discrete choice experiment

Objective

Establish maternal preferences for a third‐trimester ultrasound scan in a healthy, low‐risk pregnant population.

Design

Cross‐sectional study incorporating a discrete choice experiment.

Setting

A large, urban maternity hospital in Northern Ireland.

Participants

One hundred and forty‐six women in their second trimester of pregnancy.

Methods

A discrete choice experiment was designed to elicit preferences for four attributes of a third‐trimester ultrasound scan: health‐care professional conducting the scan, detection rate for abnormal foetal growth, provision of non‐medical information, cost. Additional data collected included age, marital status, socio‐economic status, obstetric history, pregnancy‐specific stress levels, perceived health and whether pregnancy was planned. Analysis was undertaken using a mixed logit model with interaction effects.

Main outcome measures

Women's preferences for, and trade‐offs between, the attributes of a hypothetical scan and indirect willingness‐to‐pay estimates.

Results

Women had significant positive preference for higher rate of detection, lower cost and provision of non‐medical information, with no significant value placed on scan operator. Interaction effects revealed subgroups that valued the scan most: women experiencing their first pregnancy, women reporting higher levels of stress, an adverse obstetric history and older women.

Conclusions

Women were able to trade on aspects of care and place relative importance on clinical, non‐clinical outcomes and processes of service delivery, thus highlighting the potential of using health utilities in the development of services from a clinical, economic and social perspective. Specifically, maternal preferences exhibited provide valuable information for designing a randomized trial of effectiveness and insight for clinical and policy decision makers to inform woman‐centred care.     

Methods of gestational age assessment influence the observed association between antiretroviral therapy exposure,preterm delivery,and small-for-gestational age infants: a prospective study in Cape Town,South Africa

PurposeHeterogeneous findings exist on antiretroviral therapy (ART) use in pregnancy and preterm delivery (PTD) or infants born small-for-gestational age (SGA). Whether reported differences may be explained by methods used to ascertain gestational age (GA) has not been explored.MethodsWe enrolled consecutive pregnant women attending a large primary care antenatal clinic in South Africa. Public-sector midwives assessed GA by last menstrual period (LMP) and symphysis-fundal height (SFH). Separately, if clinical GA was less than 24 weeks, ultrasound (US) was performed by a research sonographer blinded to midwife assessments. In analysis, the impact of measurement error on the association between HIV/ART status and birth outcome by GA method was assessed, and factors associated with clinical GA underestimation or overestimation identified.ResultsIn 1787 women included overall, estimated PTD incidence was 36% by LMP, 17% by SFH, and 11% by US. PTD risk was higher for HIV-infected than HIV-uninfected women using US-GA (adjusted odds ratio [aOR] 1.95; 95% CI 1.10–3.46); for LMP/SFH-GA, the associations were smaller and not significant. These findings persisted after adjustment for age, parity, height, and previous PTD. PTD risk did not vary by timing of ART initiation (before or during pregnancy) for any method. Elevated BMI and older age were associated with decreased risk of underestimation by both LMP and SFH; HIV status and obesity were associated with increased risk of overestimation by SFH. There were no differences in SGA incidence across GA methods.ConclusionsFindings for an association between HIV/ART and birth outcomes are substantially influenced by GA assessment method. With growing public health interest in this association, future research efforts should seek to standardize optimal measures of gestation.