The Impact of Exposure Misclassification on Associations Between Prepregnancy BMI and Adverse Pregnancy Outcomes

Prepregnancy BMI is a widely used marker of maternal nutritional status that relies on maternal self‐report of prepregnancy weight and height. Pregravid BMI has been associated with adverse health outcomes for the mother and infant, but the impact of BMI misclassification on measures of effect has not been quantified. The authors applied published probabilistic bias analysis methods to quantify the impact of exposure misclassification bias on well‐established associations between self‐reported prepregnancy BMI category and five pregnancy outcomes (small for gestational age (SGA) and large for gestational age (LGA) birth, spontaneous preterm birth (sPTB), gestational diabetes mellitus (GDM), and preeclampsia) derived from a hospital‐based delivery database in Pittsburgh, PA (2003–2005; n = 18,362). The bias analysis method recreates the data that would have been observed had BMI been correctly classified, assuming given classification parameters. The point estimates derived from the bias analysis account for random error as well as systematic error caused by exposure misclassification bias and additional uncertainty contributed by classification errors. In conventional multivariable logistic regression models, underweight women were at increased risk of SGA and sPTB, and reduced risk of LGA, whereas overweight, obese, and severely obese women had elevated risks of LGA, GDM, and preeclampsia compared with normal‐weight women. After applying the probabilistic bias analysis method, adjusted point estimates were attenuated, indicating the conventional estimates were biased away from the null. However, the majority of relations remained readily apparent. This analysis suggests that in this population, associations between self‐reported prepregnancy BMI and pregnancy outcomes are slightly overestimated.     

Early Gestational Weight Gain Rate and Adverse Pregnancy Outcomes in Korean Women

During pregnancy, many women gain excessive weight, which is related to adverse maternal and neonatal outcomes. In this study, we evaluated whether rate of gestational weight gain (RGWG) in early, mid, and late pregnancy is strongly associated with adverse pregnancy outcomes. A retrospective chart review of 2,789 pregnant Korean women was performed. Weights were recorded at the first clinic visit, during the screening test for fetal anomaly, and during the 50g oral glucose challenge test and delivery, to represent early, mid, and late pregnancy, respectively. A multivariate logistic regression analysis was performed to examine the relationship between RGWG and adverse pregnancy outcomes. At early pregnancy, the RGWG was significantly associated with high risk of developing gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), large for gestational age (LGA) infants, macrosomia, and primary cesarean section (P-CS). The RGWG of mid pregnancy was not significantly associated with any adverse pregnancy outcomes. The RGWG at late pregnancy was significantly associated with a lower risk of developing GDM, preterm birth and P-CS, but with a higher risk of developing LGA infants and macrosomia. When the subjects were divided into three groups (Underweight, Normal, and Obese), based on pre-pregnancy body mass index (BMI), the relationship between early RGWG and adverse pregnancy outcomes was significantly different across the three BMI groups. At early pregnancy, RGWG was not significantly associated to adverse pregnancy outcomes for subjects in the Underweight group. In the Normal group, however, early RGWG was significantly associated with GDM, PIH, LGA infants, macrosomia, P-CS, and small for gestational weight (SGA) infants, whereas early RGWG was significantly associated with only a high risk of PIH in the Obese group. The results of our study suggest that early RGWG is significantly associated with various adverse pregnancy outcomes and that proper preemptive management of early weight gain, particularly in pregnant women with a normal or obese pre-pregnancy BMI, is necessary to reduce the risk of developing adverse pregnancy outcomes.     

Optimal Timing of Delivery among Low-Risk Women with Prior Caesarean Section: A Secondary Analysis of the WHO Multicountry Survey on Maternal and Newborn Health

Objective

To investigate optimal timing of elective repeat caesarean section among low-risk pregnant women with prior caesarean section in a multicountry sample from largely low- and middle-income countries.

Design

Secondary analysis of a cross-sectional study.

Setting

Twenty-nine countries from the World Health Organization Multicountry Survey on Maternal and Newborn Health.

Population

29,647 women with prior caesarean section and no pregnancy complications in their current pregnancy who delivered a term singleton (live birth and stillbirth) at gestational age 37–41 weeks by pre-labour caesarean section, intra-partum caesarean section, or vaginal birth following spontaneous onset of labour.

Methods

We compared the rate of short-term adverse maternal and newborn outcomes following pre-labour caesarean section at a given gestational age, to those following ongoing pregnancies beyond that gestational age.

Main Outcome Measures

Severe maternal outcomes, neonatal morbidity, and intra-hospital early neonatal mortality.

Results

Odds of neonatal morbidity and intra-hospital early neonatal mortality were 0.48 (95% confidence interval [CI] 0.39–0.60) and 0.31 (95% CI 0.16–0.58) times lower for ongoing pregnancies compared to pre-labour caesarean section at 37 weeks. We did not find any significant change in the risk of severe maternal outcomes between pre-labour caesarean section at a given gestational age and ongoing pregnancies beyond that gestational age.

Conclusions

Elective repeat caesarean section at 37 weeks had higher risk of neonatal morbidity and mortality compared to ongoing pregnancy, however risks at later gestational ages did not differ between groups.     

高龄孕妇分娩新生儿出生体重及出院转归的影响因素分析

摘要 目的：探讨高龄孕妇分娩新生儿出生体重及出院转归的影响因素。方法：选择2021年01月到2022年01月与我院就诊的198例产妇作为研究对象,根据孕妇分娩时的年龄分为观察组和对照组,分娩时年龄满35周岁为高龄产妇组（98例）,分娩时年龄为20~34周岁为适龄组（100例）。比较适龄孕妇和高龄孕妇新生儿出生体重情况和新生儿住院时间,对高龄孕妇新生儿体重和新生儿出院转归影响因素进行Logistic单因素分析和多因素分析。结果：与适龄孕妇相比,高龄孕妇新生儿低出生体重儿、巨大儿发生率更高（P<0.05）,新生儿住院时间明显更长（P<0.05）。对高龄孕妇新生儿体重进行单因素分析结果显示,妊娠糖尿病、产检检查、分娩方式、是否使用催产素、分娩时麻醉方式和脐带情况与高龄孕妇新生儿体重无关（P>0.05）,孕妇年龄、孕前BMI、孕期体重增加情况、妊娠高血压、合并其他疾病状况、孕次、产次、羊水情况与高龄孕妇新生儿体重相关（P<0.05）。进行Logistic多因素回归分析结果显示,孕妇年龄、孕前BMI、孕期体重增加情况、孕次、产次、羊水情况是影响高龄孕妇新生儿出生体重的独立危险因素（P<0.05）。对新生儿出院转归情况进行单因素分析结果显示,胎次、开奶时间、喂养方式和有无接受治疗与新生儿出院转归无相关性（P>0.05）,胎龄、出生体重、Apgar评分、出生窒息史、有无伴发疾病与新生儿转归相关（P<0.05）。进行Logistic多因素分析结果显示,胎龄、出生体重、Apgar评分、出生窒息史、有无伴发病是影响新生儿出院转归的独立危险因素（P<0.05）。结论：孕妇年龄、孕前BMI、孕期体重增加情况、孕次、产次、羊水情况是影响高龄孕妇新生儿出生体重的独立危险因素。新生儿出院转归受到胎龄、出生体重、Apgar评分、出生窒息史、有无伴发病影响。     

Risk assessment adjusted for gestational age in maternal serum screening for Down's syndrome.

OBJECTIVE--To investigate the relation between errors in calculation of gestational age and assessment of risk of Down''s syndrome and to analyse the implications for screening programmes. DESIGN--Retrospective analysis of dating of gestational age by menstrual history v ultrasound scan. Computer program with maternal age and concentrations of alpha fetoprotein and free beta human chorionic gonadotrophin to calculate risk for a range of expected dates of delivery. Computer simulated prospective application of new screening programme. SETTING--Teaching hospitals in Nottingham. SUBJECTS--31,561 women with singleton pregnancies with gestational age based on routine ultrasound scan. Computer simulation of 20,000 women in three age ranges (up to 37; up to 40; all). MAIN OUTCOME MEASURES--Distribution of error between gestational age based on ultrasound scan v menstrual history. Proportion of women in the population who require precise dating of pregnancy; proportion of women who require amniocentesis. RESULTS--With gestational age derived from ultrasound scan as reference the 95% confidence interval for gestational age by menstrual history was -27 to +9 days. A screening programme for Down''s syndrome for women up to age 40 would yield a low risk (< 1:250) for this range of days in 86.0% of cases. The 14.0% of women remaining would have one or more high risk values in their report and would thus require an ultrasound scan for precise dating of the pregnancy; 30% of these--that is, 3.7% of the screened population--would be identified as high risk and require consideration for amniocentesis. CONCLUSIONS--Screening programmes for Down''s syndrome require the facility for precise dating of pregnancy to improve the accuracy of risk assessment. This can be achieved without introducing additional scans for early dating in the whole population but by selecting only those cases (about 14%) when an error in dates is likely to affect the risk of Down''s syndrome.     

Cervical cancer in pregnancy: Analysis of the literature and innovative approaches

Cervical cancer is one of the most common gynecological malignancies diagnosed during pregnancy although, fortunately, it is a rare event. In majority of cases, the management of cervical cancer in pregnant women is not different from nonpregnant women and prognosis seems not compromised by pregnancy. The association between cancer and pregnancy appears to be a significant challenge for women and specialists and the decisions about therapy must be individualized and taken by a multidisciplinary team. This review is focused on cervical cancer in pregnancy. The aim is to discuss the diagnosis, potential biomarkers and molecular aspects, therapeutic approaches, and prognosis from intraepithelial cervical neoplasia to invasive cervical cancer (early and advanced stages) in different gestational ages. We provide an overview of the current literature regarding the treatment strategies of concurrent pregnancy and cervical cancer cases and we propose some clinical advices to help clinicians to manage this condition. A mention about the effects of the conservative therapy (as conization) on fertility, the human papillomavirus vaccine in pregnant women and our center's experience with obstetrical and oncological outcomes are reported.     

Risk Factors and Birth Outcomes of Anaemia in Early Pregnancy in a Nulliparous Cohort

Background

Anaemia in pregnancy is a major public health and economic problem worldwide, that contributes to both maternal and fetal morbidity and mortality.

Objective

The aim of the study was to calculate the prevalence of anaemia in early pregnancy in a cohort of ‘low risk’ women participating in a large international multicentre prospective study (n = 5 609), to identify the modifiable risk factors for anaemia in pregnancy in this cohort, and to compare the birth outcomes between pregnancies with and without anaemia in early gestation.

Methods

The study is an analysis of data that were collected prospectively during the Screening for Pregnancy Endpoints study. Anaemia was defined according to the World Health Organization’s definition of anaemia in pregnancy (haemoglobin < 11g/dL). Binary logistic regression with adjustment for potential confounders (country, maternal age, having a marital partner, ethnic origin, years of schooling, and having paid work) was the main method of analysis.

Results

The hallmark findings were the low prevalence of anaemia (2.2%), that having no marital partner was an independent risk factor for having anaemia (OR 1.34, 95% CI 1.01-1.78), and that there was no statistically significant effect of anaemia on adverse pregnancy outcomes (small for gestational age, pre-tem birth, mode of delivery, low birth weight, APGAR score < 7 at one and five minutes). Adverse pregnancy outcomes were however more common in those with anaemia than in those without.

Conclusion

In this low risk healthy pregnant population we found a low anaemia rate. The absence of a marital partner was a non-modifiable factor, albeit one which may reflect a variety of confounding factors, that should be considered for addition to anaemia’s conceptual framework of determinants. Although not statistically significant, clinically, a trend towards a higher risk of adverse pregnancy outcomes was observed in women that were anaemic in early pregnancy.     

Estimation of gestational ages in the common marmoset (Callithrix jacchus) from published prenatal growth curves

This report compares estimated gestational ages from published cubic spline curves to gestational ages estimated retrospectively from delivery dates in 28 pregnancies from ten common marmosets (Callithrix jacchus). Both CRL- and BPD-based estimates of gestational age were closely correlated with delivery-based gestational age estimates. Of the three ultrasound machines used, the one with 16 shades of gray and a sequential linear array overestimated gestational age during early pregnancy, based on CRL measures. Measures from the other two machines (64 or 264 shades of gray; linear sector and annular array or electronic phase array) were similar and resulted in a correlation of the two estimates of gestational age of 0.94 and a mean difference between the two estimates of 0.16 days with 80% of CRL-based gestational age estimates being within ± 5 days of the delivery-based estimate. The reliability of BPD-based estimates of gestational age was strongly related to pregnancy outcome. BPD-based estimates underestimated gestational age in poor outcome pregnancies (i.e., those in which infants died within 7 days of birth) but not in good outcome pregnancies. The combined CRL- and BPD-based estimates on poor outcome pregnancies suggest that there was less growth in BPD in late gestation for those pregnancies that resulted in nonviable offspring. For good outcome pregnancies, the correlation between BPD-based and delivery-based estimates of gestational age was 0.871 and the mean difference between the two estimates was ?0.06 days with 83.3% of BPD-based estimates falling within ± 5 days of delivery-based estimates.     

Corrections for measurement error due to delayed onset of illness for case-crossover designs

Epidemiologic studies of the short-term effects of ambient particulate matter (PM) on the risk of acute cardiovascular or cerebrovascular events often use data from administrative databases in which only the date of hospitalization is known. A common study design for analyzing such data is the case-crossover design, in which exposure at a time when a patient experiences an event is compared to exposure at times when the patient did not experience an event within a case-control paradigm. However, the time of true event onset may precede hospitalization by hours or days, which can yield attenuated effect estimates. In this article, we consider a marginal likelihood estimator, a regression calibration estimator, and a conditional score estimator, as well as parametric bootstrap versions of each, to correct for this bias. All considered approaches require validation data on the distribution of the delay times. We compare the performance of the approaches in realistic scenarios via simulation, and apply the methods to analyze data from a Boston-area study of the association between ambient air pollution and acute stroke onset. Based on both simulation and the case study, we conclude that a two-stage regression calibration estimator with a parametric bootstrap bias correction is an effective method for correcting bias in health effect estimates arising from delayed onset in a case-crossover study.     

Coerced first sexual intercourse and selected reproductive health outcomes among young women in KwaZulu-Natal, South Africa

Coercion may play an important role in compelling young women to engage in sexual intercourse at an early age. With a decline in age at first intercourse and increased reporting of coercive first sex, concerns of adverse reproductive health outcomes such as unintended pregnancy and sexually transmitted infections (STIs), including HIV, have become important issues, particularly in the context of a high HIV prevalence. This paper uses data collected in 2001 from the second round of a longitudinal study of 1130 sexually experienced young women in KwaZulu-Natal to investigate the relationship between coerced first intercourse and selected reproductive health outcomes and behaviours. Nearly 46% of all sexually experienced young women had reported that their first sexual encounter had been coerced. Young women who reported being coerced at first sex were significantly more likely to be Black and living in an urban area. Those who had been coerced at first sex were also more likely to report having had an STI and having experienced unintended pregnancy, than those who had not been coerced at first sex. Coercion at first sex is an important social and public health problem that has a serious impact on the reproductive health and behaviours of young women. Interventions should directly address the issue of sexual coercion by ensuring young women are aware of their reproductive rights.     

Symptoms of an Intrauterine Hematoma Associated with Pregnancy Complications: A Systematic Review

Objective

To evaluate the predictive value of the symptoms of an intrauterine hematoma (IUH) for adverse pregnancy outcomes.

Methods

A literature review was performed with the search terms, including intrauterine/subchorionic/retroplacental/subplacental hematoma/hemorrhage/bleeding/collection/fluid, covering the period from January, 1981 to January, 2014. We just focused on the pregnancy outcomes associated with different symptoms of an IUH.

Results

It is generally agreed that a retroplacental, posterior or subchorionic in the fundus of uterus, and/or persistent IUH is associated with adverse outcomes in the ongoing pregnancy. However, the prognosis value of both volume and gestational age at diagnosis of IUH still remains controversial. Some researchers argue that a large IUH is associated with an increased risk of adverse events during pregnancy while others refuted. It is believed by some that the earlier an IUH was detected, the higher the risk for adverse outcomes would be, while no or weak association were reported by other studies. The prognostic value of the simultaneous presence of vaginal bleeding on pregnancy outcome is also controversial.

Conclusions

Both the position relative to the placenta or uterus and duration of IUH have strong predictive value on the prognosis in the ongoing pregnancy. However, the prognostic values of the IUH volume, gestational age at diagnosis and the simultaneous presence of vaginal bleeding remain controversial up to now. Moreover, most of previous reports are small, uncontrolled studies with incomplete information. Prospective, large sample, cohorts studies which take all detailed symptoms of an IUH into consideration are needed when we evaluate its clinical significance in the prognosis of pregnancy.     

A systematic review to calculate background miscarriage rates using life table analysis

The objectives of the current study were to calculate: (1) the expected rates of miscarriage by gestational week; (2) the cumulative risk of miscarriage; and (3) the remaining risk of miscarriage for gestational weeks five through 20, through a systematic review of the literature. We searched MEDLINE for articles published in English through the end of 2009. References of articles were also searched. Four studies were identified to have the three necessary pieces of information for the proposed calculations: (1) gestational age at study entry, (2) pregnancy outcome; and (3) the gestational age at which the pregnancy outcome occurred. Data were extracted from each study and Life Table Analysis Methods were conducted. Weekly miscarriage rates varied in the early gestational weeks with the highest rate documented at >20 miscarriages per 1000 women-weeks at each week of gestation prior to week 13. By week 14, the rate for all studies became relatively comparable and fell below 10 miscarriages per 1000 woman-weeks at risk and fell even lower through week 20. The cumulative risk of miscarriage for weeks 5 through 20 of gestation ranged from 11 miscarriages per 100 women to 22 miscarriages per 100 women (11-22%). Based on data from comparable study populations, a range of background miscarriage rates by week of gestation for weeks 5 through 20, the cumulative risk of miscarriage, and the remaining risk of miscarriage are presented. Wider variation of miscarriage rates and risks occurred early in gestation (<14 weeks).     

Birth weight corrected for gestational age is related to the incidence of Down's syndrome pregnancies.

Three recent studies reported that early depletion of the primordial follicle pool is likely to be an independent risk factor for Down's syndrome pregnancies. The size of the primordial follicle pool at birth is determined by oogenesis and by the rate of follicle atresia during the intra uterine period. Since intra uterine growth retardation was reported to be associated with a significantly reduced primordial follicle pool at birth, we investigated the possibility of a relation between low birth weight for gestational age and the risk of a Down's syndrome pregnancy. In a case control study, 95 women with a history of a Down's syndrome pregnancy and 85 controls provided information on their own birth weight and length of gestation. Birth weight standard deviation scores, indicating the difference in birth weight from a reference group, were significantly lower in Down's syndrome mothers than in controls. These findings illustrate that the risk of a Down's syndrome pregnancy is related to a low birth weight corrected for gestational age, possibly by a causal relation between intra uterine growth retardation and the size of the primordial follicle pool.     

Early pregnancy azathioprine use and pregnancy outcomes

BACKGROUND: Azathioprine (AZA) is used during pregnancy by women with inflammatory bowel disease (IBD), other autoimmune disorders, malignancy, and organ transplantation. Previous studies have demonstrated potential risks. METHODS: The Swedish Medical Birth Register was used to identify 476 women who reported the use of AZA in early pregnancy. The effect of AZA exposure on pregnancy outcomes was studied after adjustment for maternal characteristics that could act as confounders. RESULTS: The most common indication for AZA use was IBD. The rate of congenital malformations was 6.2% in the AZA group and 4.7% among all infants born (adjusted OR: 1.41, 95% CI: 0.98–2.04). An association between early pregnancy AZA exposure and ventricular/atrial septal defects was found (adjusted OR: 3.18, 95% CI: 1.45–6.04). Exposed infants were also more likely to be preterm, to weigh <2500 gm, and to be small for gestational age compared to all infants born. This effect remained for preterm birth and low birth weight when infants of women with IBD but without AZA exposure were used as a comparison group. A trend toward an increased risk of congenital malformations was found among infants of women with IBD using AZA compared to women with IBD not using AZA (adjusted OR: 1.42, 95% CI: 0.93–2.18). CONCLUSIONS: Infants exposed to AZA in early pregnancy may be at a moderately increased risk of congenital malformations, specifically ventricular/atrial septal defects. There is also an increased risk of growth restriction and preterm delivery. These associations may be confounded by the severity of maternal illness. Birth Defects Research (Part A), 2009. © 2009 Wiley‐Liss, Inc.     

Outcome of pregnancy in underweight women after spontaneous and induced ovulation

Low maternal weight before pregnancy and poor weight gain during pregnancy are known to result in an increased prevalence of low birthweight infants. Low body weight is also an important cause of amenorrhoea. The hypothesis that amenorrhoeic underweight women who become pregnant after induction of ovulation are more at risk of delivering low birthweight infants than underweight women who ovulate spontaneously was investigated. Forty one pregnant women in whom ovulation had been induced and 1212 in whom ovulation was spontaneous were studied. Women ovulating spontaneously whose weight was normal and who showed good weight gain during pregnancy (>450 g a week) had the lowest incidence (6%) of babies who were small for gestational age. Underweight women (body mass index <19·1) who ovulated spontaneously had a threefold increased risk of delivering babies who were small for gestational age (18%). Overall, the women in whom ovulation had been induced had an even higher risk of babies who were small for dates (25%), and this risk was greatest (54%) in those who were underweight.The outcome of pregnancy is related to weight before conception, which in many cases reflects nutritional state; lack of spontaneous ovulation indicates an increased risk of producing a small for dates infant. The most suitable treatment for infertility secondary to weight related amenorrhoea is therefore dietary rather than induction of ovulation.     

Risk factors and outcomes of maternal obesity and excessive weight gain during pregnancy

Objective:

The prevalence of overweight and obesity among women of reproductive age is increasing. We aimed to determine risk factors and maternal, fetal and childhood consequences of maternal obesity and excessive gestational weight gain.

Design and Methods:

The study was embedded in a population‐based prospective cohort study among 6959 mothers and their children. The study was based in Rotterdam, The Netherlands (2001–2005).

Results:

Maternal lower educational level, lower household income, multiparity, and FTO risk allel were associated with an increased risk of maternal obesity, whereas maternal European ethnicity, nulliparity, higher total energy intake, and smoking during pregnancy were associated with an increased risk of excessive gestational weight gain (all p‐values <0.05). As compared to normal weight, maternal obesity was associated with increased risks of gestational hypertension (OR 6.31 (95% CI 4.30, 9.26)), preeclampsia (OR (3.61, (95% CI 2.04, 6.39)), gestational diabetes (OR 6.28 (95%CI 3.01, 13.06)), caesarean delivery (OR 1.91 (95% CI 1.46, 2.50)), delivering large size for gestational age infants (OR 2.97 (95% CI 2.16, 4.08)), and childhood obesity (OR 5.02 (95% CI:2.97, 8.45)). Weaker associations of excessive gestational weight gain with maternal, fetal and childhood outcomes were observed, with the strongest effects for first trimester weight gain.

Conclusions:

Our study shows that maternal obesity and excessive weight gain during pregnancy are associated with socio‐demographic, lifestyle, and genetic factors and with increased risks of adverse maternal, fetal and childhood outcomes. As compared to prepregnancy overweight and obesity, excessive gestational weight gain has a limited influence on adverse pregnancy outcomes.     

Preconception Thyroid-Stimulating Hormone And Pregnancy Outcomes In Women With Hypothyroidism

ObjectivesMaternal hypothyroidism may adversely affect pregnancy outcomes. International practice guidelines recommend that women with hypothyroidism should attain a preconception and early gestation serum thyroid-stimulating hormone (TSH) level of <2.5 mU/L. Our objective was to ascertain what proportion of women realize this target in practice and whether a TSH level above this threshold has adverse fetal and maternal consequences.MethodsThis was an observational study of women with hypothyroidism referred to an endocrine antenatal clinic between 2008 and 2010 (n = 78; mean age, 30.4 years; range, 19 to 43 years). Thyroid profiles (free thyroxine [FT4] and TSH) before conception and through pregnancy were documented. Obstetrics outcomes were examined, including low birth weight, preterm births, preeclampsia, caesarean sections, and admissions to special care neonatal units.ResultsThyroid testing was undertaken in 80% of subjects before conception, and in 64, 94, and 96% of subjects in the first, second, and third trimesters of pregnancy, respectively. TSH >2.5 mU/L was seen in 49% of women before conception and in 68% of women in thefirst trimester. Six women were overtly hypothyroid before conception, attaining normal thyroid function at gestational ages ranging from 12 to 36 weeks. Neither the preconception nor the first postconception TSH level (>2.5 mU/L or ≤2.5 mU/L) was associated with gestational age at delivery, birth weight, or rates of caesarean section or preeclampsia.ConclusionThe majority of women with hypothyroidism do not achieve the recommended preconception and early gestation TSH targets. Preconception and early gestation TSH >2.5 mU/L was not associated with adverse fetal and maternal outcomes. Studies in larger cohorts will be required to confirm these findings, however. (Endocr Pract. 2013;19:656-662)     

Relationships of risk factors for pre-eclampsia with patterns of occurrence of isolated gestational proteinuria during normal term pregnancy

Background

Isolated gestational proteinuria may be part of the pre-eclampsia disease spectrum. Confirmation of its association with established pre-eclampsia risk factors and higher blood pressure in uncomplicated pregnancies would support this concept.

Methods

Data from 11,651 women from the Avon Longitudinal Study of Parents and Children who had a term live birth but did not have pre-existing hypertension or diabetes or develop gestational diabetes or preeclampsia were used. Proteinuria was assessed repeatedly (median 12 measurements per woman) by dipstick and latent class analysis was used to identify subgroups of the population with different patterns of proteinuria in pregnancy.

Results

Higher maternal pre-pregnancy body mass index (BMI), younger age, nulliparity and twin pregnancy were independently associated with increased odds of any proteinuria in pregnancy. Women who experienced proteinuria showed five patterns: proteinuria in early pregnancy only (≤20 weeks gestation), and onset at 21–28 weeks, 29–32 weeks, 33–36 weeks and ≥37 weeks gestation. There were higher odds of proteinuria onset after 33 weeks in obese women and after 37 weeks in nulliparous women compared with normal weight and multiparous women respectively. Smoking in pregnancy was weakly negatively associated with odds of proteinuria onset after 37 weeks. Twin pregnancies had higher odds of proteinuria onset from 29 weeks. In women with proteinuria onset after 33 weeks blood pressure was higher in early pregnancy and at the end of pregnancy.

Conclusions

Established pre-eclampsia risk factors were related to proteinuria occurrence in late gestation in healthy term pregnancies, supporting the hypothesis that isolated gestational proteinuria may represent an early manifestation of pre-eclampsia.     

The Long Term Economic Impact of Severe Obstetric Complications for Women and Their Children in Burkina Faso

This study investigates the long term economic impact of severe obstetric complications for women and their children in Burkina Faso, focusing on measures of food security, expenditures and related quality of life measures. It uses a hospital based cohort, first visited in 2004/2005 and followed up four years later. This cohort of 1014 women consisted of two main groups of comparison: 677 women who had an uncomplicated delivery and 337 women who experienced a severe obstetric complication which would have almost certainly caused death had they not received hospital care (labelled a “near miss” event). To analyze the impact of such near miss events as well as the possible interaction with the pregnancy outcome, we compared household and individual level indicators between women without a near miss event and women with a near miss event who either had a live birth, a perinatal death or an early pregnancy loss. We used propensity score matching to remove initial selection bias. Although we found limited effects for the whole group of near miss women, the results indicated negative impacts: a) for near miss women with a live birth, on child development and education, on relatively expensive food consumption and on women’s quality of life; b) for near miss women with perinatal death, on relatively expensive foods consumption and children’s education and c) for near miss women who had an early pregnancy loss, on overall food security. Our results showed that severe obstetric complications have long lasting consequences for different groups of women and their children and highlighted the need for carefully targeted interventions.     

Comparison of cohort and nested case-control designs for estimating the effect of time-varying drug exposure on the risk of adverse event in the presence of ties

Cohort and nested case-control (NCC) designs are frequently used in pharmacoepidemiology to assess the associations of drug exposure that can vary over time with the risk of an adverse event. Although it is typically expected that estimates from NCC analyses are similar to those from the full cohort analysis, with moderate loss of precision, only few studies have actually compared their respective performance for estimating the effects of time-varying exposures (TVE). We used simulations to compare the properties of the resulting estimators of these designs for both time-invariant exposure and TVE. We varied exposure prevalence, proportion of subjects experiencing the event, hazard ratio, and control-to-case ratio and considered matching on confounders. Using both designs, we also estimated the real-world associations of time-invariant ever use of menopausal hormone therapy (MHT) at baseline and updated, time-varying MHT use with breast cancer incidence. In all simulated scenarios, the cohort-based estimates had small relative bias and greater precision than the NCC design. NCC estimates displayed bias to the null that decreased with a greater number of controls per case. This bias markedly increased with higher proportion of events. Bias was seen with Breslow's and Efron's approximations for handling tied event times but was greatly reduced with the exact method or when NCC analyses were matched on confounders. When analyzing the MHT-breast cancer association, differences between the two designs were consistent with simulated data. Once ties were taken correctly into account, NCC estimates were very similar to those of the full cohort analysis.