Caroline Signore

Circulating angiogenic factors and placental abruption

OBJECTIVE: Abnormalities in circulating angiogenic factors have been reported in diseases of abnormal placentation, such as preeclampsia and intrauterine growth restriction. Our objective was to determine whether circulating angiogenic factors are altered in another placental vascular disease, abruptio placentae. METHODS: In a nested case-control study of nulliparous pregnancies, we examined levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) in serum collected prospectively from 31 women who later developed placental abruption and from 31 normal control subjects. All serum specimens were collected before the onset of hypertension or abruption and before labor or delivery. Serum angiogenic factors were compared within 3 gestational age windows: early (20 weeks or less), middle (21–32 weeks), and late (33 weeks or more) pregnancy. RESULTS: During early pregnancy women who developed placental abruption had lower PlGF and higher sFlt-1 concentrations and higher sFlt-1/PlGF ratios than women with normal pregnancies. In mid-pregnancy these differences became greater, reaching statistical significance for PlGF concentration (431 versus 654 pg/mL, P<.01) and the sFlt-1/PlGF ratio (25.3 versus 2.5, P<.01). When the women with placental abruption were subdivided into those who did (n=10) and those who did not (n=21) develop preeclampsia or gestational hypertension, significant alterations in angiogenic factors were noted only in women who later developed hypertension in pregnancy. Among these women, PlGF concentrations were decreased in mid-pregnancy (160 versus 723 pg/mL, P<.001), and the mid-pregnancy sFlt-1/PlGF ratio was increased (70.1 versus 2.3, P=.001). CONCLUSION: Serum levels of the proangiogenic factor PlGF were decreased, and those of the antiangiogenic ratio sFlt-1/PlGF were increased in nulliparous women who subsequently developed hypertension and placental abruption. LEVEL OF EVIDENCE: II-2

Infant Sleeping Arrangements and Practices During the First Year of Life

OBJECTIVES. Our goal was to examine the sleeping arrangements for infants from birth to 1 year of age and to assess the association between such arrangements and maternal characteristics. METHODS. Responses to the 3-, 6-, 9-, and 12-month questionnaires from the Infant Feeding Practices Study II were analyzed to assess sleep arrangements, including bed sharing, the latter defined as mother ever (in a given time frame) slept with the infant on the same sleeping surface for nighttime sleep. Women were also asked about the reasons for bed sharing or not bed sharing. RESULTS. Approximately 2300 women responded at 3 months, and 1800 at 12 months. At 3 months, 85% of the infants slept in the same room as their mother, and at 12 months that rate was 29%. At 3 months, 26% of the mothers did not use the recommended supine position for their infants nighttime sleep. The rate of noncompliance increased to 29% by 6 months and 36% by 12 months. The bed-sharing rates were 42% at 2 weeks, 34% at 3 months, and 27% at 12 months. Approximately two thirds of those who bed shared with their infant also shared the bed with their husband or partner, and 5% to 15% shared it with other children. The major reasons for bed sharing were to calm a fussy infant, facilitate breastfeeding, and help the infant and/or mother sleep better. The major reasons for not lying down with the infant were safety concerns. Non-Hispanic black mothers were more likely than non-Hispanic white mothers to use nonsupine infant sleep positions and to bed share. CONCLUSIONS. More than one third of the women in this cohort were noncompliant with safe-sleeping guidelines when their infant was 3 months old. Health care providers need to advise parents of current recommendations and discuss the risks and benefits of their choices for infant sleeping practices.

Neonatal Morbidity and Mortality After Elective Cesarean Delivery

This article explores the effects of elective cesarean delivery (ECD) at term on neonatal morbidity and mortality. Available data have limitations, and do not provide conclusive evidence regarding the safety of planned ECD versus planned vaginal delivery. Some data suggest an association between ECD and increased neonatal respiratory morbidity and lacerations, and possibly decreased central and peripheral nervous system injury. Potentially increased risks of neonatal mortality with ECD at term may be counterbalanced by risks for fetal demise in ongoing pregnancies. Patients and physicians considering ECD should review competing risks and benefits; further research is needed to inform these discussions.

Evaluation of common genetic variants in 82 candidate genes as risk factors for neural tube defects

BackgroundNeural tube defects (NTDs) are common birth defects (~1 in 1000 pregnancies in the US and Europe) that have complex origins, including environmental and genetic factors. A low level of maternal folate is one well-established risk factor, with maternal periconceptional folic acid supplementation reducing the occurrence of NTD pregnancies by 50-70%. Gene variants in the folate metabolic pathway (e.g., MTHFR rs1801133 (677 C > T) and MTHFD1 rs2236225 (R653Q)) have been found to increase NTD risk. We hypothesized that variants in additional folate/B12 pathway genes contribute to NTD risk.MethodsA tagSNP approach was used to screen common variation in 82 candidate genes selected from the folate/B12 pathway and NTD mouse models. We initially genotyped polymorphisms in 320 Irish triads (NTD cases and their parents), including 301 cases and 341 Irish controls to perform case–control and family based association tests. Significantly associated polymorphisms were genotyped in a secondary set of 250 families that included 229 cases and 658 controls. The combined results for 1441 SNPs were used in a joint analysis to test for case and maternal effects.ResultsNearly 70 SNPs in 30 genes were found to be associated with NTDs at the p < 0.01 level. The ten strongest association signals (p-value range: 0.0003–0.0023) were found in nine genes (MFTC, CDKN2A, ADA, PEMT, CUBN, GART, DNMT3A, MTHFD1 and T (Brachyury)) and included the known NTD risk factor MTHFD1 R653Q (rs2236225). The single strongest signal was observed in a new candidate, MFTC rs17803441 (OR = 1.61 [1.23-2.08], p = 0.0003 for the minor allele). Though nominally significant, these associations did not remain significant after correction for multiple hypothesis testing.ConclusionsTo our knowledge, with respect to sample size and scope of evaluation of candidate polymorphisms, this is the largest NTD genetic association study reported to date. The scale of the study and the stringency of correction are likely to have contributed to real associations failing to survive correction. We have produced a ranked list of variants with the strongest association signals. Variants in the highest rank of associations are likely to include true associations and should be high priority candidates for further study of NTD risk.

MTHFD1 R653Q Polymorphism Is a Maternal Genetic Risk Factor for Severe Abruptio Placentae

This study examined the relationship between folate/homocysteine‐related genetic polymorphisms: MTHFD1 1958G → A (R653Q), MTHFR 677C → T (A222V), MTHFR 1298A → C (E429A), and risk of severe abruptio placentae. We genotyped 62 women with a pregnancy history complicated by severe abruptio placentae and 184 control pregnancies. Analysis of the MTHFD1 1958G → A (R653Q) polymorphism showed increased frequency of the ‘QQ’ homozygote genotype in pregnancies affected by severe abruptio placentae compared to control pregnancies (odds ratio 2.85 (1.47–5.53), P = 0.002). In contrast to previous reports, the MTHFR polymorphisms 677C → T (A222V) and 1298A → C (E429A) were not associated with abruptio placentae risk in our cohort, when analyzed either independently or in combination. We conclude that women who are ‘QQ’ homozygote for the MTHFD1 1258G → A (R653Q) polymorphism are almost three times more likely to develop severe abruptio placentae during their pregnancy than women who are ‘RQ’ or ‘RR.’ Published 2005 Wiley‐Liss, Inc.

Antenatal Testing – A Reevaluation: Executive Summary of a Eunice Kennedy Shriver National Institute of Child Health and Human Development Workshop

In August 2007, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institutes of Health Office of Rare Diseases, the American College of Obstetricians and Gynecologists, and the American Academy of Pediatrics cosponsored a 2-day workshop to reassess the body of evidence supporting antepartum assessment of fetal well-being, identify key gaps in the evidence, and formulate recommendations for further research. Participants included experts in obstetrics and fetal physiology and representatives from relevant stakeholder groups and organizations. This article is a summary of the discussions at the workshop, including synopses of oral presentations on the epidemiology of stillbirth and fetal neurological injury, fetal physiology, techniques for antenatal monitoring, and maternal and fetal indications for monitoring. Finally, a synthesis of recommendations for further research compiled from three breakout workgroups is presented.

Influence of Bedsharing Activity on Breastfeeding Duration Among US Mothers

IMPORTANCE Some professional associations advocate bedsharing to facilitate breastfeeding, while others recommend against it to reduce the risk of sudden infant death syndrome and suffocation deaths. A better understanding of the quantitative influence of bedsharing on breastfeeding duration is needed to guide policy. OBJECTIVE To quantify the influence of bedsharing on breastfeeding duration. DESIGN, SETTING, AND PARTICIPANTS Longitudinal data were from the Infant Feeding Practices Study II, which enrolled mothers while pregnant and followed them through the first year of infant life. Questionnaires were sent at infant ages 1 to 7, 9, 10, and 12 months, and 1846 mothers answered at least 1 question regarding bedsharing and were breastfeeding at infant age 2 weeks. EXPOSURES Bedsharing, defined as the mother lying down and sleeping with her infant on the same bed or other sleeping surfaces for nighttime sleep or during the major sleep period. MAIN OUTCOMES AND MEASURES Survival analysis to investigate the effect of bedsharing on duration of any and exclusive breastfeeding. RESULTS Longer duration of bedsharing, indicated by a larger cumulative bedsharing score, was associated with a longer duration of any breastfeeding but not exclusive breastfeeding, after adjusting for covariates. Breastfeeding duration was longer among women who were better educated, were white, had previously breastfed, had planned to breastfeed, and had not returned to work in the first year postpartum. CONCLUSIONS AND RELEVANCE Multiple factors were associated with breastfeeding, including bedsharing. Given the risk of sudden infant death syndrome related to bedsharing, multipronged strategies to promote breastfeeding should be developed and tested.

Circulating soluble endoglin and placental abruption

Our objective was to investigate whether serum concentrations of a novel anti‐angiogenic factor, soluble endoglin (sEng), could predict placental abruption.

Delivery After Previous Cesarean: Long-Term Outcomes in the Child

In subsequent pregnancies after a cesarean delivery, women must choose between attempting to deliver vaginally or undergoing another cesarean delivery. Information relevant to this choice includes the long-term benefits and harms to the baby. In this article we discuss the relationship of mode of delivery (planned trial of labor, either with or without vaginal delivery, or elective repeat cesarean delivery) and long-term outcomes, including brachial plexus palsy, neurodevelopmental impairment, and asthma. No randomized trials are available that relate directly to the choice of delivery method after previous cesarean. Observational studies suggest that cesarean delivery might be associated with a greater risk of asthma, caused perhaps by altered gut colonization, increased risk of neonatal respiratory disease, decreased gestational age at birth or decreased likelihood of breastfeeding. By contrast, vaginal delivery after a previous cesarean delivery is associated with greater risks of neurodevelopmental impairment and upper-extremity motor impairment, caused, respectively, by greater risks of perinatal hypoxic-ischemic encephalopathy and brachial plexus injury. Available information does not provide a precise estimate of the relative risks for infants delivered after a trial of labor versus elective cesarean delivery.

The need for targeted weight-control approaches in young women and men.

In this issue of the American Journal of Preventive Medicine, Brown et al.1 investigate the role that pregnancy plays in 10-year weight gain among a cohort of Australian women who were initially aged 18–23 years. Their results, based on women who were mostly nulliparous and unmarried at baseline, are consistent with previous findings suggesting that childbearing is a significant predictor of later weight gain.2–4 More than 40% of pregnant women in the U.S. gain weight in excess of recommended amounts; the IOM recently updated their guidelines for how much weight women should gain during pregnancy.5 Once gained, excess pregnancy weight is difficult to lose and may be associated with an increased risk of developing obesity, diabetes, and cardiovascular disease (CVD) later in life.6,7 Given that women who enter pregnancy overweight or obese are at higher risk of adverse pregnancy outcomes, such as preeclampsia, gestational diabetes, fetal macrosomia, cesarean delivery8 and postpartum weight retention,6 it would be beneficial for women to attain a healthy weight before they consider pregnancy. However, about 50% of U.S. women of childbearing age are overweight or obese,9 and nearly 50% of pregnancies are unplanned.10 Few researchers have tried to disentangle the role of pregnancy from other factors. Brown et al.1 also conclude that living with a partner but not having a child is associated with higher 10-year weight gain than not having a partner and child. In another recent study, young adults who transitioned from being single or dating to cohabitating or married were more likely to become obese over the next 5–6 years than those not making that transition.11 These two findings suggest that living with a partner itself in addition to pregnancy puts young women at higher risk of obesity. The results of a research by The and Gordon-Larsen11 apply also to young men, but the relationship between parenting and weight gain among men is less well studied. Early adulthood is a time of life-changing events, such as moving away from family and entering the work force, in addition to marriage and parenting. The changing social and environmental context associated with these life changes may profoundly affect weight gain for both young women and men. Indeed, young adults gain 1–2 pounds per year, with the largest weight gain—almost 3 pounds/year—occurring between the ages of 20 and 29 years.12 Excess weight gain early in adulthood is associated with later, more adverse levels of CVD risk factors, such as hypertension, dyslipidemia, and diabetes.13,14 Despite the high risk for weight gain early in adulthood and the subsequent increased risk of adverse outcomes, few studies have tested behavioral interventions aimed at young adults. A few studies have focused on preventing excessive weight gain during pregnancy15–18 or returning to pre-pregnancy weight19,20 but for the most part, these studies have been small, with high attrition and limited generalizability. A similarly small number of studies have targeted weight control among young adults in general.21–23 Although eligible for adult weight-loss studies, young adult participants usually have less weight loss and higher attrition rates than older participants.24 In general, the interventions tested to date have had varying success, suggesting that a better understanding of influences and barriers is pivotal in developing interventions that will appeal to young adults. As with older adults, influences on obesity-related behaviors—particularly dietary intake and physical activity—are multi-factorial, including physiology, family, peers, community, culture, and the environment. However, such influences may differ in their importance to young adults. For example, young adults may be more sensitive to peer pressure, have fewer economic resources, and may be less motivated to adopt healthy behaviors because they perceive health consequences to be distal. New parents may face unique barriers, such as time and energy constraints due to balancing child care, work, and home responsibilities. On the other hand, pregnant women and new parents may be more motivated to control their own weight if they realize that such changes may also benefit their children’s health.25 The National Heart, Lung, and Blood Institute and the Eunice Kennedy Shriver National Institute of Child Health and Human Development recently funded six studies that may begin to fill the interventional research gap related to weight control in young adults. Recognizing that weight-control approaches will need to be targeted toward this age group, each study will conduct formative research to refine the proposed intervention, recruitment, retention, and adherence strategies. Incorporating what was learned during the formative phase, each study will conduct a 2-year RCT to test the efficacy of the behavioral interventions that address weight loss, prevention of weight gain, or prevention of excessive peripartum weight gain. Specific target populations include pregnant and postpartum women, community college or university students, and young adults trying to quit smoking. The trials will have racial/ethnic, gender, and socioeconomic diversity across the study populations. While the interventions build on proven approaches for older adults, they are adapted to be more appealing to young adults. To do this, most plan to use technology-driven methods such as mobile phones, social networks, Internet programs, and web-based curricula. The use of technology to deliver interventions may also reduce participant burden, a critical consideration for pregnant women and new parents. These interventions have the potential to be practical, cost-effective, and easily disseminated on a broad scale if they are proven efficacious. Successful interventions can not only help young adults achieve and maintain a healthy weight, but may prevent or delay the development of many chronic diseases and other obesity-related adverse outcomes. Moreover, by improving health behaviors in adults of childbearing age, these interventions may lead to healthier behaviors and weights for the next generation of children.