Obstetrical and neonatal outcomes among pregnancies complicated by hyperparathyroidism.

PURPOSE: Severe hypercalcemia resulting from hyperparathyroidism may result in adverse perinatal outcomes. The objective of this study was to evaluate maternal and neonatal outcomes among pregnant women with hyperparathyroidism using a population database. METHODS: A retrospective cohort study was conducted using data from the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample from 1999-2015. ICD-9 codes were used to identify women diagnosed with hyperparathyroidism during pregnancy. Perinatal outcomes between pregnant women with and without hyperparathyroidism were compared. Multivariate logistic regression, controlling for age, race, income, insurance type, hospital location, and comorbidities, evaluated the effect of hyperparathyroidism on perinatal outcomes. RESULTS: Of 13,792,544 deliveries included over the study period, 368 were to women with hyperparathyroidism. The overall incidence of hyperparathyroidism was 2.7/100,000 births, increasing from 1.6 to 5.2/100,000 births over the study period (p < 0.0001). Women with hyperparathyroidism were older and had more comorbidities, such as obesity, and pre-gestational hypertension and diabetes. Relative to the comparison group, women with hyperparathyroidism were more likely to deliver preterm, OR 1.69 (95% CI 1.24-2.29), to develop preeclampsia, 3.14 (2.30-4.28), and to deliver by cesarean, 1.69 (1.36-2.09). Infants born to mothers with hyperparathyroidism were more likely to be growth restricted, 1.83 (1.08-3.07), and to be diagnosed with a congenital anomaly, 4.21 (2.09-8.48). CONCLUSION: Hyperparathyroidism during pregnancy is associated with a significant increase in adverse perinatal outcomes, including preeclampsia, preterm delivery, fetal growth restriction, and congenital anomalies. As such, pregnancies among women with hyperparathyroidism should be considered high-risk, and specialized care is recommended in order to minimize maternal and neonatal morbidity.

Spontaneous Rectus Sheath Hematoma in Pregnancy: A Case Report.

CONTEXTE: L'hématome du grand droit (HGD) est une cause rare mais importante de douleur abdominale pendant la grossesse. CAS: Une femme de 32 ans a consulté à 316 semaines de grossesse en raison de douleurs abdominales du côté droit. L'échographie a révélé une structure hétérogène compatible avec un HGD. Une prise en charge s'est composée d'un traitement symptomatique au moyen d'analgésiques et d'un suivi obstétrical et échographique. L'échographie a révélé la résorption de l'HGD après 6 semaines. À 38 semaines de grossesse, la patiente a subi un déclenchement artificiel du travail pour cause de pré-éclampsie et a donné naissance à une fille en bonne santé. CONCLUSION: Notre étude de cas présente un HGD spontané survenu à 32 semaines de grossesse, lequel a été pris en charge par traitement symptomatique. La grossesse s'est soldée par un accouchement à terme.

Exploratory study of the interest of MR susceptibility-weighted imaging for the pre-operative assessment of pelvic endometriosis extent.

OBJECTIVE: To evaluate the performance of magnetic resonance imaging (MRI) with susceptibility-weighted imaging (SWI) in the assessment of endometriosis. MATERIAL AND METHODS: This prospective study was performed during the diagnostic step or the pre-operative assessment of endometriosis, between June 2017 and April 2018. The MRI was conducted with a 3T MRI device; protocol included T2W, T1W, with and without fat-saturation sequences completed with a SWI sequence: T2-star weighted angiography (SWAN). The diagnostic performance values of MRI and inter-observer agreement were first evaluated with a conventional MR protocol and then with the complementary SWAN sequence by 2 readers. MRI results were correlated with surgical findings in patients who underwent laparoscopy. RESULTS: 74 patients were included in the study, and among them 10 patients were treated by laparoscopy. 81% of the endometriosis lesions had signal losses on the SWAN sequence related to hemorrhagic character whereas only 52% of the lesions had T1-weighted hyperintense implants. Diagnostic performance of the MRI examination was improved by the use of the SWAN sequence compared to the conventional MR protocol (Se = 94% and Spe = 73% in complete protocol and Se = 88% and Spe = 69% in conventional protocol), especially for the involvement of torus uterinus, utero-sacral ligament and retro-cervical site. An excellent interobserver agreement (қ-value = 0,94) was noted between the two readers. CONCLUSION: SWI can improve the diagnostic accuracy of MRI by allowing the detection of hemorrhagic character of endometriosis lesions.

FDG PET/CT in Pediatric Neurolymphomatosis.

An 8-year-old girl presented with back and leg pain and left arm and leg paresis. Lumbar puncture was suggestive of lymphocytic meningitis without identified organism. A second lumbar puncture demonstrated a large number of lymphoid B cells, with positive immunohistochemical staining for CD20 and CD25, proving the diagnosis of neurolymphomatosis. Brain and spine MRI demonstrated involvement of cervical and lumbosacral nerve roots. FDG PET/CT showed multiple bone metastases in addition to nerve involvement. Postchemotherapy FDG PET/CT demonstrated complete metabolic response.

A nationwide evaluation of spontaneous coronary artery dissection in pregnancy and the puerperium.

OBJECTIVE: Spontaneous coronary artery dissection (SCAD) is a rare and potentially lethal cause of myocardial infarction (MI). The purpose of our study was to estimate the prevalence and maternal outcomes of pregnancies complicated by SCAD. MATERIALS AND METHODS: A population-based cohort study on all births identified in the Healthcare Cost and Utilization Project from 2008 to 2012. Disease prevalence was calculated and logistic regression was used to estimate the adjusted odds ratio (aOR) for risk factors and different maternal complications. RESULTS: A total of 4 363 343 pregnancy-related discharges were evaluated. 79 cases of SCAD were identified resulting in a prevalence of 1.81 per 100 000 pregnancies. The mean maternal age at the time of diagnosis was 33.4 years (±5.2). Chronic hypertension (aOR, 2.67; 95% CI 1.18 to 6.03), lipid profile abnormalities (aOR, 48.22; 95% CI 24.25 to 95.90), chronic depression (aOR, 3.56; 95% CI 1.43 to 8.83) and history of migraine (aOR, 3.93; 95% CI 1.52 to 10.17) were associated with an elevated risk for SCAD. MI was diagnosed in 66 (85.5%) cases of SCAD with anterior and subendocardial territories being the most common locations. Thirty one patients (40%) with SCAD underwent angioplasty with the majority receiving stents, which was associated with a longer hospital stay than those treated conservatively or with bypass. CONCLUSIONS: SCAD is a rare aetiology of MI; risk factors and outcomes are illustrated in the current study. The puerperium is an important period for the development of pregnancy-related SCAD. Careful evaluation of pregnant and postpartum women with chest pain is warranted, especially if these risk factors are identified.

Risk factors for high and low placental weight.

BACKGROUND: Placental weight is an independent predictor of adverse perinatal outcome. However, risk factors for high and low placental weight are poorly understood. The objective of this study was to identify maternal, placental, and umbilical cord determinants of placental weight, before and after accounting for birthweight. METHODS: This cohort study of 87,600 singleton births at the Royal Victoria Hospital in Montreal, Canada assessed the relationship between maternal, placental, and umbilical cord characteristics and placental weight (standardised for sex and gestational age). We separately examined risk factors for high (z-score >+1) and low (z-score <-1) placental weight. Multivariable logistic regression was used to study associations after adjusting for confounders and further adjusting for birthweight. RESULTS: Chronic hypertension was associated with low placental weight {relative risk (RR) 2.1 [95% confidence interval (CI) 1.8, 2.4] and 1.8 [95% CI 1.5, 2.1] before and after accounting for birthweight}, while pre-eclampsia was associated with low placenta weight before, but not after adjustment for birthweight. Anaemia and gestational diabetes were linked with high placental weight (RRs 1.2-1.4, respectively) before and after adjustment for birthweight, while smoking was linked with high placental weight only after adjustment for birthweight (RR 1.4 [95% CI 1.3, 1.5]). Placental and cord determinants of high placental weight included chorioamnionitis, chorangioma/chorangiosis, circumvallate placenta, marginal cord insertion, and other cord abnormalities. CONCLUSIONS: The broad range of risk factors for high placental weight suggests multiple aetiologic pathways. Future work should seek to understand the pathways by which the placenta adapts to unfavourable intrauterine conditions, which may provide insights into potential therapies.

Effect of induced abortions on early preterm births and adverse perinatal outcomes.

OBJECTIVES: To examine the association between prior induced abortions and prematurity and to explore potential mechanisms for a relationship, including second trimester pregnancy losses and infections. METHODS: We conducted a retrospective review of the records of all women who delivered between April 2001 and March 2006 using data from the McGill Obstetric and Neonatal Database. Exposure was categorized as having had no prior induced abortions, one prior induced abortion, or two or more prior induced abortions. Our primary outcome was gestational age at delivery, categorized as < 24 weeks, < 26 weeks, < 28 weeks, < 32 weeks and < 37 weeks. Secondary outcomes were intrapartum fever, NICU admission, and use of tocolysis. RESULTS: A total of 17 916 women were included in the study. Of these 2276 (13%) had undergone one prior induced abortion, and 862 (5%) had undergone two or more prior induced abortions. Women with a prior induced abortion were more likely to be smokers and to consume alcohol, and were less likely to be married. Women who reported one prior induced abortion were more likely to have premature births by 32, 28, and 26 weeks; adjusted odds ratios were 1.45 (95% CI 1.11 to 1.90), 1.71 (95% CI 1.21 to 2.42), and 2.17 (95% CI 1.41 to 3.35), respectively. This association was stronger for women with two or more previous induced abortions. Prior induced abortion was associated with an increased requirement for tocolysis in subsequent pregnancies, but there was no association between prior induced abortions and NICU admission, intrapartum fever, and preterm premature rupture of membranes. CONCLUSION: Our study showed a significant increase in the risk of preterm delivery in women with a history of previous induced abortion. This association was stronger with decreasing gestational age.

Increased risk of preterm premature rupture of membranes at early gestational ages among maternal cigarette smokers.

OBJECTIVE: To examine the effect of cigarette smoking during pregnancy on the development of preterm premature rupture of membranes (PPROM) categorized by gestational age. METHODS: We conducted a retrospective cohort study of 17,961 births using data from the McGill Obstetric and Neonatal Database between years 2001 and 2006. Our exposure was defined according to self-reported maternal cigarette smoking status categorized as nonsmoker, smoker of 1 to 10 cigarettes per day, and smoker of > 10 cigarettes per day. The outcome was measured as incidence of premature rupture of membranes (PROM) among gestational age categories of < 28, < 32, < 37, and > 37 weeks. Unconditional logistic regression analysis and Wald test for trend were used to estimate the adjusted risk of PPROM according to smoking status. RESULTS: Among the study population, 640 cases of PPROM (<37 weeks) and 40 cases of PROM (>37 weeks). After adjusting for confounding variables, smoking > 10 cigarettes per day was associated with an increased risk of PPROM at < 28 weeks (odds ratio [OR] 5.28; 95% confidence interval [CI] 2.20 to 12.7); < 32 weeks (OR 2.36; 95% CI 1.09 to 5.11; < 37 weeks (OR 1.97; 95% CI 1.32 to 2.94); and > 37 weeks (OR 3.19; 95% CI 0.92 to 11.0). Smoking 1 to 10 cigarettes per day was not associated with a significant risk of PPROM at any gestational age. CONCLUSION: Heavy cigarette smoking increases the risk of PPROM more so at early gestational age than at term.

Incidence, risk factors, and obstetrical outcomes of women with breast cancer in pregnancy.

Breast cancer in pregnancy is a rare condition. The objective of our study was to describe the incidence, risk factors, and obstetrical outcomes of breast cancer in pregnancy. We conducted a population-based cohort study on 8.8 million births using data from the Healthcare Cost and Utilization Project - Nationwide Inpatient Sample from 1999-2008. The incidence of breast cancer was calculated and logistic regression analysis was used to evaluate the independent effects of demographic determinants on the diagnosis of breast cancer and to estimate the adjusted effect of breast cancer on obstetrical outcomes. There were 8,826,137 births in our cohort of which 573 cases of breast cancer were identified for an overall 10-year incidence of 6.5 cases per 100,000 births with the incidence slightly increasing over the 10-year period. Breast cancer appeared to be more common among women >35 years of age, odds ratio (OR)=3.36 (2.84-3.97); women with private insurance plans, OR=1.39 (1.10-1.76); and women who delivered in an urban teaching hospital, OR=2.10 (1.44-3.06). After adjusting for baseline characteristics, women with pregnancy-associated breast cancer were more likely to have an induction of labor, OR=2.25 (1.88, 2.70), but similar rates of gestational diabetes, preeclampsia, instrumental deliveries, and placental abruption. The incidence of breast cancer in pregnancy appears higher than previously reported with women over 35 being at greatest risk. Aside from an increased risk for induction of labor, women with breast cancer in pregnancy have similar obstetrical outcomes.

Anti-D in Rh(D)-negative pregnant women: are at-risk pregnancies and deliveries receiving appropriate prophylaxis?

OBJECTIVE: Although anti-D prophylaxis has greatly reduced the rate of Rh-immunization, there remain women who sensitize during or after pregnancy because of inadequate prophylaxis. The purpose of this study was to compare adherence to prophylaxis recommendations for antenatal and postnatal anti-D immunoglobulin administration. METHODS: We conducted a retrospective cohort study of all pregnancies recorded at the Royal Victoria Hospital between 2001 and 2006 to determine the rates of antenatal and postnatal prophylaxis in Rh(D)-negative women. We compared adherence to anti-D prophylaxis recommendations between our institution's physician-dependent antenatal approach and the protocol-based postpartum approach. Logistic regression analysis was used to estimate the odds ratio and 95% confidence intervals of determinants of non-adherence to current recommendations for anti-D prophylaxis. RESULTS: Antenatal administration was analyzed in 1868 pregnancies in eligible Rh-negative women. Among these women, 85.7% received appropriate antenatal prophylaxis and 98.5% of eligible women received appropriate postnatal prophylaxis. Factors independently associated with non-adherence to antepartum prophylaxis included first visit in the third trimester (P < 0.001), transfer from an outside hospital (P = 0.03), and physician licensing before 1980 (P = 0.04). CONCLUSION: Unlike hospital-based protocol-dependent systems, physician-dependent systems for antenatal anti-D prophylaxis remain subject to errors of omission. A more standardized system is needed to ensure effective antenatal prophylaxis.

Placental weight for gestational age and adverse perinatal outcomes.

OBJECTIVE: The fetoplacental ratio has been used conventionally to study the contribution of the placenta to fetal growth restriction. However, this measure is problematic because a normal fetoplacental ratio can reflect birth weight and placental weight that are both normal, both low, or both high. The objective of this study was to examine the independent association between placental weight for gestational age and perinatal mortality or serious neonatal morbidity. METHODS: A sex- and gestational age-specific placental weight z score was calculated for a cohort of 87,600 singleton births at the Royal Victoria Hospital in Montreal, Canada, 1978-2007. The relationship between placental weight z score and adverse perinatal outcomes (stillbirth, neonatal death, 5-minute Apgar score lower than 7, seizures, or respiratory morbidity) was examined using logistic regression. Multivariable models examined whether the relationship was independent of birth weight and other pregnancy risk factors. RESULTS: : After controlling for birth weight, fetuses with a low placental weight z score were at significantly increased risk of stillbirth (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.4-2.6, percent population attributable risk 17.8%). In contrast, adverse neonatal outcomes were significantly more likely among those with high placental weight z scores (OR 1.4, 95% CI 1.2-1.7, percent population attributable risk 5% for any serious neonatal morbidity). Similar trends were observed after further adjusting for pregnancy risk factors. CONCLUSION: Placental weight for gestational age is an independent risk factor for adverse perinatal outcomes, above and beyond the known association with birth weight. The mechanisms behind the opposing effects of placental weight z score on risk of stillbirth compared with adverse neonatal outcomes require further elucidation. LEVEL OF EVIDENCE: III.

Higher caesarean section rates in women with higher body mass index: are we managing labour differently?

BACKGROUND: Higher body mass index has been associated with an increased risk of Caesarean section. The effect of differences in labour management on this association has not yet been evaluated. METHODS: We conducted a cohort study using data from the McGill Obstetrics and Neonatal Database for deliveries taking place during a 10-year period. Women's BMI at delivery was categorized as normal (20 to 24.9), overweight (25 to 29.9), obese (30 to 39.9), or morbidly obese (≥ 40). We evaluated the effect of the management of labour on the need for Caesarean section using unconditional logistic regression models. RESULTS: Data were available for 11 922 women, of whom 2289 women had normal weight, 5663 were overweight, 3730 were obese, and 240 were morbidly obese. After adjustment for known confounding variables, increased BMI category was associated with an overall increase in the use of oxytocin and in the use of epidural analgesia, and with a decrease in use of forceps and vacuum extraction among second stage deliveries. Higher BMI was also found to be associated with earlier decisions to perform a Caesarean section in the second stage of labour. When adjusted for these differences in the management of labour, the increasing rate of Caesarean section observed with increasing BMI category was markedly attenuated (P < 0.001). CONCLUSION: Women with an increased BMI are managed differently in labour than women of normal weight. This difference in management in part explains the increased rate of Caesarean section observed with higher BMI.

Effect of maternal age on the risk of stillbirth: a population-based cohort study on 37 million births in the United States.

The objective of our study was to evaluate the incidence and effect of maternal age on the risk of stillbirth. We conducted a population-based cohort study using the Centers for Disease Control and Prevention's "Linked Birth-Infant Death" and "Fetal Death" data files. We excluded all births of gestational age under 24 weeks and those with reported congenital malformations. We estimated the adjusted effect of maternal age on the risk of stillbirth using logistic regression analysis. There were 37,504,230 births that met study criteria, of which 130,353 (3.5/1,000) were stillbirths. Rates of stillbirth remained constant throughout the 10 years. As compared with women between the ages of 25 and 30, decreasing maternal age was associated with the following risk of stillbirth: odds ratio (OR) 0.95 (95% confidence interval [CI] 0.93 to 0.97) for ages 20 to 25; OR 0.97 (95% CI 0.94 to 0.99) for ages 15 to 20; and OR 1.32 (95% CI 1.18 to 1.47) for ages <15. Increasing maternal age was associated with an increasing risk of stillbirth: OR 1.02 (95% CI 0.99 to 1.04) for ages 30 to 35, OR 1.25 (95% CI 1.21 to 1.28) for ages 35 to 40, OR 1.60 (95% CI 1.53 to 1.67) for ages 40 to 45, and OR 2.22 (95% CI 1.91 to 2.53) for ages >45. Although the overall risk is low, the risk of stillbirth increases considerably in women at the extremes of the reproductive age spectrum. Antenatal surveillance may be justified in these women.

Pregnancy-associated breast cancer: a review for the obstetrical care provider.

Breast cancer is uncommon in pregnancy, but obstetrical care providers should nevertheless be familiar with the presenting signs and symptoms. The incidence of breast cancer in pregnancy and the postpartum period ranges from 2.3 to 40 cases per 100 000 women. Over 90% of patients with breast cancer in pregnancy or during lactation present with a palpable mass, and most often (84%) these are self-reported by patients. Less frequently, breast cancer will present as breast erythema, breast swelling, bloody nipple discharge, or local or distant metastasis. The histology of tumours appears to be similar in women who are pregnant or recently delivered and in age-matched women who are not pregnant. However, the stage of disease at diagnosis is more advanced in women who are pregnant or recently delivered and consequently incurs a worst prognosis, likely due to a delay in diagnosis. Although the majority of palpable breast masses are benign, breast examinations should routinely be performed in pregnant women, and identified masses should be promptly evaluated.

Effect of prior cesarean delivery on neonatal outcomes.

AIMS: To examine the effect of a prior cesarean delivery on neonatal outcomes. METHODS: We conducted a retrospective cohort study on all women with a prior livebirth who delivered at the Royal Victoria Hospital between 2001 and 2006. We defined our exposure as a positive history for cesarean delivery and used unconditional logistic regression analysis to estimate the adjusted effect of a previous cesarean delivery on adverse neonatal outcomes. RESULTS: A total of 18,673 births took place of which 9708 were in women with a prior livebirth (77.0% with no previous cesarean delivery and 23.0% with a previous cesarean delivery). As compared to newborns delivered by mothers with no prior cesarean delivery, increasing number of prior cesarean deliveries was associated with an increasing risk of preterm birth [odds ratio (OR) 1.23, 95% confidence interval (CI) 1.09-1.39]; respiratory distress syndrome (OR 3.54, 95% CI 2.02-5.91); and admission to the neonatal intensive care unit (OR 1.41, 95% CI 1.25-1.60). These findings were predominantly due to differences in gestational age and mode of delivery. CONCLUSION: Having a prior cesarean delivery is associated with an increased risk of adverse neonatal outcomes. Adverse neonatal outcomes in subsequent pregnancies is additional evidence to suggest that unless specifically indicated, cesarean delivery should be avoided.

Does education level influence the decision to undergo elective repeat caesarean section among women with a previous caesarean section?

OBJECTIVE: Patient education level has been shown to affect health care outcomes in a variety of clinical contexts. The aim of this study was to evaluate whether maternal education level influences women to plan elective repeat Caesarean section rather than attempt a vaginal birth after Caesarean. METHODS: We conducted a retrospective cohort study of women with a previous Caesarean section who delivered at the Royal Victoria Hospital between 2001 and 2006. Education level was stratified as follows: /= 16 years (university degree). We used unconditional logistic regression to calculate age-adjusted estimates of the risk of having a planned Caesarean section. RESULTS: Among 18 673 deliveries in our cohort, 1915 were in women with a previous Caesarean section. Of these, 12.6% had a high school degree or less, 38.3% had some college or university education, and 49.1% had a university degree. Compared with women whose maximum education was a high school diploma, there was a higher rate of planned Caesarean section in women with some college or university education (OR 1.38; 95% CI 1.00 to 1.89, P = 0.047) and in women with a university degree (OR 1.42; 95% CI 1.04 to 1.94, P = 0.03). CONCLUSION: Higher education appears to be associated with an increased rate of elective repeat Caesarean section. Whether this is due to patient differences or physician bias, physicians should be aware of this disparity and should attempt to provide unbiased informed consent for all women regardless of their level of education.

An international trial of antioxidants in the prevention of preeclampsia (INTAPP).

OBJECTIVE: We sought to investigate whether prenatal vitamin C and E supplementation reduces the incidence of gestational hypertension (GH) and its adverse conditions among high- and low-risk women. STUDY DESIGN: In a multicenter randomized controlled trial, women were stratified by the risk status and assigned to daily treatment (1 g vitamin C and 400 IU vitamin E) or placebo. The primary outcome was GH and its adverse conditions. RESULTS: Of the 2647 women randomized, 2363 were included in the analysis. There was no difference in the risk of GH and its adverse conditions between groups (relative risk, 0.99; 95% confidence interval, 0.78-1.26). However, vitamins C and E increased the risk of fetal loss or perinatal death (nonprespecified) as well as preterm prelabor rupture of membranes. CONCLUSION: Vitamin C and E supplementation did not reduce the rate of preeclampsia or GH, but increased the risk of fetal loss or perinatal death and preterm prelabor rupture of membranes.

Investigating socio-economic disparities in preterm birth: evidence for selective study participation and selection bias.

Selective study participation can theoretically lead to selection bias. We explored this issue in the context of a multicentre cohort study of socio-economic disparities in preterm birth. Women with singleton pregnancies were recruited from four large Montreal maternity hospitals and invited to return for an interview, vaginal examination and venepuncture at 24-26 weeks of gestation. We compared the observed preterm birth rate (ultrasound confirmed) among the 5146 cohort women to that expected based on all 108 724 Montreal Census Metropolitan Area (CMA) singleton births for 1998-2000. The observed preterm birth rate in the study cohort was 5.1%, compared with 6.3% in the CMA (P < 0.001) (unadjusted morbidity ratio [95% CI] = 0.80 [0.71, 0.90]). Within each stratum of maternal education and neighbourhood income (the latter based on postal code matched links to the 2001 Canadian census), cohort women had substantially lower rates of preterm birth than women from the CMA. No significant association between socio-economic status (SES) and preterm birth was observed in the study cohort, except among 'indicated' (non-spontaneous) cases. The association between neighbourhood income and preterm birth was biased to the null in the study cohort, with adjusted odds ratios in the poorest vs. richest quintiles of 1.01 [0.63, 1.64] in the cohort vs. 1.28 [1.18, 1.39] in the CMA, although no such bias was observed for the association with maternal education assessed at the individual level. We speculate that the lower-than-expected preterm birth rate and attenuated association between neighbourhood income and preterm birth may be related to selective participation by women more psychologically invested in their pregnancies. Investigators should consider the potential for biased associations in pregnancy/birth cohort studies, especially associations based on SES or race/ethnicity, and carry out sensitivity analyses to gauge their effects.

Common variants of the glial cell-derived neurotrophic factor gene do not influence kidney size of the healthy newborn.

Glial cell-derived neurotrophic factor (GDNF) plays an important role in renal development, serving as a trophic factor for outgrowth of the ureteric bud and its continued arborisation. Our previous studies have shown that common variants of the human paired-box 2 (PAX2) gene (a transcriptional activator of GDNF) and rearranged during transfection (RET) gene (encoding the cognate receptor for GDNF) are associated with a subtle reduction in the kidney size of newborns. Since heterozygosity for a mutant GDNF allele causes mild renal hypoplasia and modest hypertension in mice, we considered the possibility that common variants of the GDNF gene might also contribute to renal hypoplasia in humans. We studied the relationship between newborn renal size or umbilical cord cystatin C and 19 common GDNF gene variants [minor allele frequency (MAF) >5%], three single nucleotide polymorphisms (SNPs) related to a putative PAX binding site and one rare SNP (rs36119840 A/G) which changes an amino acid (R93W), based on data from the haplotype map of the human genome (HapMap). However, none of these 23 SNPs was associated with reduced newborn kidney size or function. Among the 163 Caucasians in our cohort, none had the R93W allele.