Adjustment For Maternal Characteristics Research Articles

Maternal cardiovascular function at mid-gestation is related to placental angiogenesis.

To investigate whether placental function, reflected in the levels of angiogenic factors, is associated with maternal cardiac function and hemodynamic responses at 19 to 24 weeks' gestation after adjustment for maternal risk factors and pregnancy complications. Prospective study on women with singleton pregnancies attending Kings' College Hospital, London, UK for a routine hospital visit at 19-24 weeks' gestation. We recorded maternal characteristics and measured mean arterial pressure, maternal heart rate, serum placental growth factor and soluble fms-like tyrosine kinase 1 (sFLT-1).We also performed maternal echocardiogram to assess cardiac output and peripheral vascular resistance as well as indices of diastolic and systolic function. Our cohort included 4006 women.Lower placental growth factor (PlGF) values were significantly associated with higher mean arterial pressure (MAP) (p<0.001), lower maternal heart rate (p<0.001), lower mitral valve s' velocity (p= 0.027) and higher left atrial volume (p=0.022) after adjustment for maternal characteristics and pregnancy complications. sFLT-1 was positively related to relative wall thickness (p= 0.012), whereas sFLT-1/ PlGF ratio was negatively associated with mitral valve A (p= 0.006) and positively associated with left atrial volume (p= 0.015) and MAP (p= 0.004). The magnitude of these associations was similar in the subgroup of women without any risk factors from their obstetric and medical history. A continuous link of moderate strength between angiogenic factors and subclinical maternal cardiac function alterations is present at mid-gestation, independently of preexisting maternal risk factors and pregnancy complications. Impaired placental function appears to be related to a mild systolic and diastolic dysfunction and cardiac remodeling. This article is protected by copyright. All rights reserved.

P-767 Urogenital defects in live births to women dispensed clomiphene citrate: A study within a whole of population birth cohort

Abstract Study question Is the risk of urogenital defects increased in live births where clomiphene citrate is known to have been dispensed by a pharmacist to the individual? Summary answer The risk of urogenital defects is elevated in singletons, and approximately doubled in male babies among women dispensed clomiphene citrate, as compared to unexposed women. What is known already Clomiphene citrate (CC) has been used for ovulation induction since 1967 &amp; is both inexpensive and largely effective. However, CC is a selective estrogen receptor modulator (SERM), which is a class of drugs with the potential for endocrine disruption during fetal development. The link between urogenital defects and CC has previously been reported by ourselves and others. Whether the link continues to exist where individual level pharmaceutical prescribing and dispensing patterns are clearly ascertained has not been determined. Secondly, the interaction of prescribed clomiphene citrate functioning as an endocrine disruptor by fetal sex has not undergone formal statistical testing. Study design, size, duration A population-based cohort study of South Australia was assembled by linking all records from the state-wide perinatal registry for births between July 2003 and December 2011, including defects coded to ICD9 and BPA, with Commonwealth government data on pharmaceutical dispensing in the national Pharmaceutical Benefits Scheme (PBS), which includes individual level prescribing and dispensing of drugs for ovulation induction, including clomiphene citrate. Participants/materials, setting, methods We analysed de-identified pregnancy outcome data for all births in South Australia, linked to individual level national prescription data, to examine the prevalence of urogenital birth defects (&amp;gt;20 weeks gestation) for births occurring between July 2003 and December 2011following clomiphene citrate dispensing, with 5-years follow-up for defect notifications. Multivariate analysis in STATA within a Secure Unified Research Environment (SURE) was used to calculate odds ratios, adjusted for maternal confounders and socioeconomic circumstance. Main results and the role of chance We examined 2,264 singleton live births where women were dispensed clomiphene citrate for infertility. Births among women dispensed clomiphene citrate, compared to those without this exposure, had increased urogenital defects (odds ratio (OR) = 1.73, CI = 1.34 - 2.24). This association was slightly reduced after adjustment for maternal characteristics that were potential confounders: age, socio-economic status (based on postcode of residence), Aboriginal ethnicity, born outside Australia in low or middle income country, parity, smoking, pre-existing diabetes or hypertension, pregnancy-induced hypertension and pre-eclampsia (OR = 1.66, CI = 1.28 -, 2.15). There was evidence of an interaction with fetal sex, such that males were at particular risk. Sex-by-clomiphene interaction Male 1.92 (1.47, 2.52) Female 0.88 (0.37, 2.14) Test for interaction χ2(1) = 2.72; p = 0.09 The observed main effects are unlikely to be due to chance, and the sex-specific effect is biologically plausible, but limited in power. Further, there were 280 babies from multiple pregnancies to women exposed to clomiphene citrate that were excluded due to statistical limitations. Limitations, reasons for caution Our data report pharmacy dispensing, but not observed consumption, although infertile women are highly motivated to take this drug and over 5% of pregnancies were multiples, consistent with extensive use. The analysis for interactions and for multiples is currently restricted by power, which may resolve as the cohort number increases. Wider implications of the findings Clomiphene citrate (CC) may be a potent endocrine disruptor inducing urogenital defects, particularly in males. This is important as CC continues to be a WHO essential drug and a first line treatment globally, but with largely unmonitored use and without any industry initiated prospective safety study. Trial registration number Not applicable

Association between social vulnerability profiles, prenatal care use and pregnancy outcomes

BackgroundEvaluating social vulnerability is a challenging task. Indeed, former studies demonstrated an association between geographical social deprivation indicators, administrative indicators, and poor pregnancy outcomes.ObjectiveTo evaluate the association between social vulnerability profiles, prenatal care use (PCU) and poor pregnancy outcomes (Preterm birth (PTB: <37 gestational weeks (GW)), small for gestational age (SGA), stillbirth, medical abortion, and late miscarriage).MethodsRetrospective single center study between January 2020 and December 2021. A total of 7643 women who delivered a singleton after 14 GW in a tertiary care maternity unit were included. Multiple component analysis (MCA) was used to assess the associations between the following social vulnerabilities: social isolation, poor or insecure housing conditions, not work-related household income, absence of standard health insurance, recent immigration, linguistic barrier, history of violence, severe dependency, psychologic vulnerability, addictions, and psychiatric disease. Hierarchical clustering on principal component (HCPC) from the MCA was used to classify patients into similar social vulnerability profiles. Associations between social vulnerability profiles and poor pregnancy outcomes were tested using multiple logistic regression or Poisson regression when appropriate.ResultsThe HCPC analysis revealed 5 different social vulnerability profiles. Profile 1 included the lowest rates of vulnerability and was used as a reference. After adjustment for maternal characteristics and medical factors, profiles 2 to 5 were independently associated with inadequate PCU (highest risk for profile 5, aOR = 3.14, 95%CI[2.33–4.18]), PTB (highest risk for profile 2, aOR = 4.64, 95%CI[3.80–5.66]) and SGA status (highest risk for profile 5, aOR = 1.60, 95%CI[1.20–2.10]). Profile 2 was the only profile associated with late miscarriage (adjusted incidence rate ratio (aIRR) = 7.39, 95%CI[4.17–13.19]). Profiles 2 and 4 were independently associated with stillbirth (highest association for profile 2 (aIRR = 10.9, 95%CI[6.11–19.99]) and medical abortion (highest association for profile 2 (aIRR = 12.65, 95%CI[5.96–28.49]).ConclusionsThis study unveiled 5 clinically relevant social vulnerability profiles with different risk levels of inadequate PCU and poor pregnancy outcomes. A personalized patient management according to their profile could offer better pregnancy management and reduce adverse outcomes.

Impact of State Prioritization of Safe Infant Sleep Programs on Supine Sleep Positioning for Non-Hispanic White and Non-Hispanic Black Infants.

Investigate whether safe infant sleep prioritization by states through the Title V Maternal and Child Block Grant in 2010 differentially impacted maternal report of supine sleep positioning (SSP) for Non-Hispanic White (NHW) and Non-Hispanic Black (NHB) U.S.-born infants. We analyzed retrospective cross-sectional data from the Pregnancy Risk Assessment Monitoring System (PRAMS) from 2005 to 2015 from 4 states: WV and OK (Intervention) and AR and UT (Control). PRAMS is a population-based surveillance system of maternal perinatal experiences which is linked to infant birth certificates. Piece-wise survey linear regression models were used to estimate the difference in the change in slopes of SSP percents in the pre- (2005-2009) and post- (2011-2015) periods, controlling for maternal and infant characteristics. Models were also stratified by race/ethnicity. From 2005 to 2015, for NHW infants, SSP improved from 61.5% and 70.2% to 82.8% and 82.3% for intervention and control states, respectively. For NHB infants, SSP improved from 30.6% and 26.5% to 64.5% and 53.1% for intervention and control states, respectively. After adjustment for maternal characteristics, there was no difference in the rate of SSP change from the pre- to post- intervention periods for either NHW or NHB infants in intervention or control groups. Compared with control states that did not prioritize safe infant sleep in their 2010 Title V Block Grant needs assessment, intervention states experienced no difference in SSP improvement rates for NHW and NHB infants. While SSP increased for all infants during the study period, there was no causal relationship between states' prioritization of safe infant sleep and SSP improvement. More targeted approaches may be needed to reduce the racial/ethnic disparity in SSP and reduce the risk for sleep-associated infant death. · Supine sleep positioning improved for Black and White infants in the U.S.. · State prioritization of safe infant sleep did not directly impact SSP for NHB or NHW infants.. · More targeted approaches may be needed to reduce racial/ethnic disparities in safe sleep practices.

Slowing of fetal growth and elevated maternal serum sFLT1:PlGF are associated with early term spontaneous labor

BackgroundThe physiological control of human parturition at term is unknown.ObjectiveThis study aimed to test the hypothesis that slowing of fetal growth or elevated maternal serum levels of markers of placental hypoxia in late gestation will be associated with earlier term labor.Study DesignWe observed 2208 women having first births and performed serial blinded ultrasonography and immunoassay of soluble fms-like tyrosine kinase-1 and placenta growth factor. We estimated the probability of spontaneous delivery from 37 weeks of gestational age concerning (1) fetal growth between 20 and 36 weeks of gestational age and (2) the maternal serum soluble fms-like tyrosine kinase-1–to–placenta growth factor ratio measured at approximately 36 weeks of gestational age. Data were analyzed using logistic regression and Cox regression.ResultsFetal size at 36 weeks of gestational age was not independently associated with the timing of delivery at term. However, there was an inverse relationship between fetal growth between 20 weeks of gestational age and 36 weeks of gestational age and the probability of spontaneous labor at 37 to 38 weeks’ gestation (hazard ratio [95% confidence interval] for a 50 percentile increase in abdominal circumference growth velocity, 0.60 [0.47–0.78]; P=.0001). This association was weaker at 39 to 40 weeks’ gestation (0.83 [0.74–0.93]; P=.0013), and there was no association at ≥41 weeks’ gestation. Very similar associations were observed for estimated fetal weight growth velocity. There was a positive relationship between soluble fms-like tyrosine kinase-1–to–placenta growth factor ratio and the probability of spontaneous labor at 37 to 38 weeks’ gestation (hazard ratio [95% confidence interval] for a 50 percentile increase in soluble fms-like tyrosine kinase-1–to–placenta growth factor ratio, 3.05 [2.32–4.02]; P<.0001). This association was weaker at 39 to 40 weeks’ gestation (1.46 [1.30–1.63]; P<.0001), and there was no association at ≥41 weeks’ gestation. Adjustment for maternal characteristics was without material effect on any of these associations.ConclusionSlowing of fetal growth and biomarkers of placental insufficiency were associated with an increased probability of early onset of spontaneous term labor. We speculated that progressive placental insufficiency may be a physiological phenomenon that occurs with advancing gestational age near and at term and promotes the initiation of labor.

Relationship between ophthalmic artery Doppler and maternal cardiovascular function.

In mid-gestation, the finding of an increase in the ophthalmic artery second to first peak of systolic velocity ratio (PSV ratio) provides useful prediction of subsequent development of pre-eclampsia (PE). The objective of this study of an unselected population at 19-23 weeks' gestation was to gain a better understanding of the factors that influence ophthalmic artery Doppler by examining the possible association between the PSV ratio and maternal cardiovascular function. This was a prospective observational study in women attending for a routine hospital visit at 19 + 1 to 23 + 3 weeks' gestation. This visit included assessment of flow velocity waveforms from the maternal ophthalmic arteries and assessment of maternal cardiovascular function. The following nine cardiovascular indices were examined: E/A ratio; E/e' ratio; myocardial performance index; global longitudinal systolic strain; left ventricular ejection fraction; peripheral vascular resistance; left ventricular cardiac output; left ventricular mass indexed for body surface area; and mean arterial pressure. The ophthalmic artery PSV ratio and the nine cardiovascular indices were converted to either log10 multiples of the median (MoM) values or deviations from the median (deltas) values after adjustment for maternal characteristics and elements of medical history. Regression analysis was then used to examine the significance of the association between PSV ratio delta and MoM or delta values of each cardiovascular index in the total population and in the subgroup that developed PE. The study population of 2853 pregnancies contained 76 (2.7%) that developed PE. In the total population, there were significant but weak associations between the PSV ratio and most of the cardiovascular indices, with r-values of < 0.1, except for mean arterial pressure with r = 0.178. In the subgroup that developed PE, a moderately strong association between the PSV ratio and left ventricular mass indexed for body surface area was noted (r = 0.308). The findings of this study suggest that Doppler assessment of PSV ratio in the ophthalmic artery provides information about peripheral vascular status. The increase in PSV ratio in women who develop PE is associated with increased afterload and an increase in left ventricular thickness. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Maternal Serum Antioxidants in Mid Pregnancy and Risk of Preterm Delivery and Small for Gestational Age Birth: Results from a Prospective Pregnancy Cohort.

Background: Preterm delivery (PTD) and poor fetal growth are major contributors to neonatal mortality and morbidity that can extend from birth onward. Although overt maternal nutrient deficiencies are associated with adverse pregnancy outcomes, such deficiencies are rare in developed countries. However, some evidence suggests that even within the normal range, higher levels of antioxidant nutrients are protective against adverse pregnancy outcomes. Materials and Methods: Using data from the prospective Pregnancy Outcomes and Community Health (POUCH) Study (n = 301 preterm; n = 246 term), we examined associations between maternal blood levels of selected antioxidants and pregnancy outcomes. Serum collected at 16-27 weeks' gestation was analyzed for carotenoids, retinol, and α- and γ-tocopherol. Using weighted polytomous regression, these nutrient concentrations were assessed in relation to (1) PTD (<37 weeks gestation) overall and grouped as spontaneous or medically indicated; and (2) small for gestational age (SGA) defined as birthweight-for-gestational age <10th percentile of a national reference population. Results: Women with total serum carotenoids in the upper quartile (Q4) had significantly lower odds of medically indicated PTD compared with women in the lower quartiles (Q1-Q3) even after adjustment for maternal characteristics (aOR = 0.4; 95% CI: 0.2-0.9). Odds ratios for SGA were consistently ≤0.5 among women with any of the serum nutrients in Q4 as compared with Q1-Q3, but final models did not reach statistical significance. Conclusion: Results support the possibility that high maternal serum antioxidants and/or the larger dietary or lifestyle pattern they represent may play a protective role in preventing adverse pregnancy outcomes.

Maternal age and risk of low birth weight and premature birth in children conceived through medically assisted reproduction. Evidence from Finnish population registers.

STUDY QUESTIONDoes the risk of low birth weight and premature birth increase with age among mothers who conceive through medically assisted reproduction (MAR)?SUMMARY ANSWERAmong MAR mothers, the risk of poorer birth outcomes does not increase with maternal age at birth except at very advanced maternal ages (40+).WHAT IS KNOWN ALREADYThe use of MAR treatments has been increasing over the last few decades and is especially diffused among women who conceive at older ages. Although advanced maternal age is a well-known risk factor for adverse birth outcomes in natural pregnancies, only a few studies have directly analysed the maternal age gradient in birth outcomes for MAR mothers.STUDY DESIGN, SIZE, DURATIONThe base dataset was a 20% random sample of households with at least one child aged 0–14 at the end of 2000, drawn from the Finnish population register and other administrative registers. This study included children who were born in 1995–2000, because the information on whether a child was conceived through MAR or naturally was available only from 1995 onwards.PARTICIPANTS/MATERIALS, SETTING, METHODSThe outcome measures were whether the child had low birth weight (LBW, <2500 g at birth) and whether the child was delivered preterm (<37 weeks of gestation). Conceptions through MAR were identified by examining data on purchases of prescription medication from the National Prescription Register. Linear probability models were used to analyse and compare the maternal age gradients in birth outcomes of mothers who conceived through MAR or naturally before and after adjustment for maternal characteristics (i.e. whether the mother suffered from acute/chronic conditions before the pregnancy, household income and whether the mother smoked during pregnancy).MAIN RESULTS AND THE ROLE OF CHANCEA total of 56 026 children, 2624 of whom were conceived through MAR treatments, were included in the study. Among the mothers who used MAR to conceive, maternal age was not associated with an increased risk of LBW (the overall prevalence was 12.6%) at ages 25–39. For example, compared to the risk of LBW at ages 30–34, the risk was 0.22 percentage points lower (95% CI: −3.2, 2.8) at ages 25–29 and was 1.34 percentage points lower (95% CI: −4.5, 1.0) at ages 35–39. The risk of LBW was increased only at maternal ages ≥40 (six percentage points, 95% CI: 0.2, 12). Adjustment for maternal characteristics only marginally attenuated these associations. In contrast, among the mothers who conceived naturally, the results showed a clear age gradient. For example, compared to the risk of LBW (the overall prevalence was 3.3%) at maternal ages 30–34, the risk was 1.1 percentage points higher (95% CI: 0.6, 1.6) at ages 35–39 and was 1.5 percentage points higher (95% CI: 0.5, 2.6) at ages ≥40. The results were similar for preterm births.LIMITATIONS, REASON FOR CAUTIONA limited number of confounders were included in the study because of the administrative nature of the data used. Our ability to reliably distinguish mothers based on MAR treatment type was also limited.WIDER IMPLICATIONS OF THE FINDINGSThis is the first study to analyse the maternal age gradient in the risk of adverse birth outcomes among children conceived through MAR using data from a nationally representative sample and controlling for important maternal health and socio-economic characteristics. This topic is of considerable importance in light of the widespread and increasing use of MAR treatments.STUDY FUNDING/COMPETING INTEREST(S)Funding for this project was provided by the European Research Council (grant no. 803959 MARTE to Alice Goisis and grant no. 336475 COSTPOST to Mikko Myrskylä). E.S. reports personal fees from Theramex, personal fees from Merck Serono, personal fees from Health Reimbursement Arrangement, non-financial support from Merck Serono and grants from Ferring, grants from Theramex, outside the submitted work. The remaining authors have no competing interests.TRIAL REGISTRTION NUMBERN/A

Association of maternal developmental disorder traits with child maltreatment

Abstract Objective Maternal mental disorders are known risk factors for child mistreatment. However, little is known about the involvement of maternal developmental disorder traits. The aim of this study was to examine maternal traits related to Pervasive Developmental Disorder (PDD) and Attention Deficit Hyperactivity Disorder (ADHD), and their possible association with child maltreatment. Methods Maternal PDD and ADHD were assessed through a self-administered questionnaire (N = 846) during mid-pregnancy using the Pervasive Developmental Disorders Autism Society Japan Rating Scale (PARS) and Adult ADHD Self-Report Scale (ASRS). The mothers completed another questionnaire on child mistreatment when the offspring was approximately 18 months of age. The associations between maternal PDD and ADHD traits and child maltreatment score were analyzed using linear regression models adjusted for covariates. Results Mothers who exhibited stronger PDD traits showed significantly higher child maltreatment score, even after adjustment for maternal characteristics at baseline and ADHD traits. At the same time, ADHD traits were significantly associated with child maltreatment after adjustment of covariates, although the association became non-significant after adjustment of PDD traits. Conclusions Mothers who showed PDD and ADHD traits during pregnancy were more likely to maltreat their children. It is essential to educate mothers with such traits with appropriate, easy-to-follow childcare instructions, preferably in simple language combined with pictorial aids. Key messages Maternal developmental disorder traits are risk factor of child maltreatment. Specific parenting training intervention for mothers with developmental disorders are needed.

The Impact of Severe Maternal Morbidity on Very Preterm Infant Outcomes

To estimate the prevalence of severe maternal morbidity among very preterm births and determine its association with very preterm infant mortality and morbidity. This study used New York City Vital Statistics birth and death records linked with maternal and newborn discharge abstract data for live births between 2010 and 2014. We included 6901 infants without congenital anomalies born between 240/7 and 326/7 weeks of gestation. Severe maternal morbidity was identified as life-threatening conditions or life-saving procedures. Outcomes were first-year infant mortality, severe neonatal morbidity (bronchopulmonary dysplasia, severe necrotizing enterocolitis, stage 3-5 retinopathy of prematurity, and intraventricular hemorrhage grades 3-4), and a combined outcome of death or morbidity. Twelve percent of very preterm live-born infants had a mother with severe maternal morbidity. Maternal and pregnancy characteristics associated with occurrence of severe maternal morbidity were multiparity, being non-Hispanic black, and preexisting health conditions, but gestational age and the percentage small for gestational age did not differ. Infants whose mothers experienced severe maternal morbidity had higher first-year mortality, 11.2% vs 7.7% without severe maternal morbidity, yielding a relative risk of 1.39 (95% CI: 1.14-1.70) after adjustment for maternal characteristics, preexisting comorbidities, pregnancy complications, and hospital factors. Severe neonatal morbidity was not associated with severe maternal morbidity. Severe maternal morbidity is an independent risk factor for mortality in the first year of life among very preterm infants after consideration of other maternal and pregnancy risk factors.

Risk of miscarriage in women conceiving after medically assisted reproduction with an ultrasound-verified viable pregnancy at 6-8 weeks' gestation.

What is the risk of miscarriage after a viable fetus verified on ultrasound at 6-8 weeks' gestation among women who conceive with medically assisted reproduction (MAR), stratified by type of fertility treatment? A nationwide register-based cohort study of women identified in the Danish ART-Registry with a viable singleton pregnancy at 6-8 weeks' gestation between 2007 and 2010 (n = 10,011). Women were identified from The Danish Fetal Medicine Database (DFMD), which holds information on early (between 6-8 and 11-14 weeks) and late (between 11-14 and 22 weeks) miscarriages. The late miscarriage rate was compared with a control group of naturally conceived pregnancies with a viable fetus at 11-14 weeks' gestation from 2008 to 2010, identified in the DFMD (n = 146,932). In the MAR1 cohort, the overall miscarriage rate was 11.8% (1091/9261) after an ultrasound verified viable pregnancy at 6-8 weeks' gestation. Most miscarriages occurred before the 11-14-week scan (1035/1091 [94.9%]). The early miscarriage rate was slightly higher in women who conceived with frozen embryo transfer compared with intrauterine insemination (IUI), corresponding to an adjusted OR of 1.31 (1.02 to 1.68). We found no significant risk associated with IVF and intracytoplasmic sperm injection compared with IUI pregnancies. The late miscarriage rate was 0.8% in women conceiving with MAR and 0.6% among controls (P = 0.013). After adjustment for maternal characteristics, none of the fertility treatment types were associated with an increased risk of miscarriage compared with naturally conceiving women.

Maternal Serum Lipid Trajectories and Association with Pregnancy Loss and Length of Gestation.

We characterized lipid trajectories and investigated lipids and rate of pregnancy lipid change with the risk of pregnancy loss or preterm delivery <37 weeks. In a secondary analysis of 337 women with one to two prior losses assigned to placebo in a randomized controlled trial at four centers (2007-2012), cholesterol, low- and high-density lipoprotein cholesterol (HDL-C), and triglycerides were measured up to 6 months prepregnancy (time 0) and pregnancy up to 7 visits. Trajectories were created using linear mixed models. Multivariable logistic regression with adjustment for maternal characteristics and cholesterol was performed. Lipids decreased from prepregnancy to 4 to 5 weeks, followed by an increase, and were biphasic or triphasic depending on the lipid component. Between 4 and 8 weeks, for every 1-unit increase in HDL-C, there was a 22% decreased odds of loss <14 weeks (odds ratio: 0.78; 95% confidence interval: 0.60, 0.99) and 24% decreased odds of loss or preterm delivery 14 to <37 weeks (odds ratio: 0.76; 95% confidence interval: 0.60, 0.96). There were no associations with other lipid components or other time points. An impaired rise of HDL-C early in pregnancy may signal maladaptation to pregnancy that is associated with pregnancy loss or preterm delivery.

Obstetric and neonatal complications among women with autoimmune disease

BackgroundThe impact of autoimmune diseases on pregnancy remains understudied on a population level. Examination of obstetric and neonatal outcomes among women with autoimmune disease and their infants can provide important insights for clinical management. MethodsAutoimmune diseases and outcomes were identified using medical records. Cesarean delivery, preterm birth, preeclampsia, small for gestational age (SGA), neonatal intensive care (NICU) admission, neonatal respiratory distress syndrome (RDS), and perinatal mortality risk was assessed. Poisson regression with robust standard errors estimated relative risks (RR) and 95% confidence intervals (95% CI) with adjustment for maternal characteristics and other chronic conditions. ResultsWomen with T1DM were at increased risk for nearly all outcomes including RDS (RR: 3.62; 95% CI: 2.84, 4.62), perinatal mortality (RR: 2.35; 95% CI: 1.12, 4.91), cesarean delivery (RR: 2.16; 95% CI: 2.02, 2.32) and preterm birth (RR: 3.52; 95% CI: 3.17, 3.91). Women with SLE also had higher risk for preterm delivery (RR: 2.90; 95% CI: 2.42, 3.48) and RDS (RR:2.99; 95% CI: 1.99, 4.51) as did women with Crohn's (cesarean delivery RR:1.31, 95% CI: 1.08, 1.60; preterm delivery RR: 1.84, 95% CI: 1.37, 2.49. RA increased risk for SGA (RR:1.66; 95% CI: 1.08, 2.55). Conclusion(s)Despite the heterogeneity in autoimmune diseases, we observed elevated preterm birth risk for most women with autoimmune disease. SLE and T1DM appeared to confer increased risk for a wide range of adverse outcomes.

Effects of maternal folic acid supplementation during pregnancy on infant neurodevelopment at 1month of age: a birth cohort study in China.

This study aimed to explore effects of maternal folic acid (FA) supplementation during pregnancy on neurodevelopment in 1-month-old infants and to determine whether effects may be related to maternal circulating inflammatory cytokine concentrations. This birth cohort study recruited 1186 mother-infant pairs in Tianjin, China, between July 2015 and July 2017. The women completed interviewer-administered questionnaires on their lifestyles and FA supplementation during pregnancy. Neurodevelopment was assessed in 1-month-old infants using a standard neuropsychological examination table. In 192 women, serum homocysteine (Hcy) and inflammatory cytokine concentrations were measured at 16-18weeks of gestation. The infants whose mothers took FA supplements during pregnancy had a significantly higher development quotient (DQ) compared with those whose mothers were non-users (P < 0.05). After adjustment for maternal characteristics, supplementary FA use for 1-3months, 3-6months, and > 6months were associated with the increases of 7.7, 11.0, and 7.4 units in the scale of infant DQ score compared with women reporting no supplement use, respectively (P < 0.05). FA supplementation was associated with a decreased serum concentration of Hcy (β = [Formula: see text] 0.19), which was correlated with women's serum inflammatory cytokine concentrations at 16-18weeks of gestation (β = 0.57). Serum inflammatory cytokine concentrations were inversely related to DQ score in the 1-months-old offspring (β = [Formula: see text] 0.22). Maternal FA supplementation during pregnancy favors neurodevelopment in the offspring at 1-month-old. This association may be mediated by changes in serum Hcy and inflammatory cytokine concentrations throughout pregnancy.

Opioid Use and Pregnancy Outcomes in Women With a Hypertensive Disorder of Pregnancy [31C

INTRODUCTION: Opioid use in pregnancy is increasing dramatically and is associated with poor maternal and neonatal outcomes. We sought to evaluate the relationship between opioid use and pregnancy outcomes among women with hypertensive disorders in pregnancy. METHODS: Retrospective cohort study among subjects with a hypertensive disorder of pregnancy that delivered ≥23 weeks gestation at a single institution (October '13-April '18). After IRB approval, subjects were stratified into two groups by opioid use (heroin, methadone or Subutex): current vs. non-users (never, quit prior to or during pregnancy). Differences were analyzed by Fisher's exact, t-test, and logistic regression, with α=0.05. RESULTS: From 10,833 deliveries, 1,487 (13.7%) were classified with a hypertensive disorder of pregnancy. 41 subjects (2.8%) actively used opioids during pregnancy, 1,098 (73.8%) were non-users and 348 (23.4%) were excluded due to unknown opioid use. Subjects using opioids were more likely to be covered by public insurance and using other substances. There were no differences in final hypertensive diagnosis for opioid users vs. non-users (p=0.26), although opioid users more often had severe diastolic blood pressure (≥110 mmHg) compared to non-users (p=0.012). Opioid use was associated with both adverse maternal and neonatal outcomes, which remained significant after adjustment for maternal characteristics and other substance use (aOR: 2.99, p=0.033 and aOR: 3.13, p=0.009, respectively). CONCLUSION: Among women with a hypertensive disorder of pregnancy, opioid use is associated with a 2-3 times increased odds for both adverse maternal and neonatal outcomes compared to non-users. These findings highlight the need to limit opioid use in pregnancy.

A contemporary amniotic fluid volume chart for the United States: The NICHD Fetal Growth Studies–Singletons

Amniotic fluid is essential to normal fetal development and is estimated clinically with ultrasound scanning to identify pregnancies that are at risk for poor perinatal outcome. Our goal was to develop a United States standard for amniotic fluid volume that is estimated by the amniotic fluid index and single deepest pocket. We performed a planned secondary analysis of a multicenter observational study of 2334 low-risk women with normal singleton gestations from 1 of 4 self-reported racial/ethnic groups. Eligible women had confirmed first-trimester dating criteria with health status, lifestyles, and medical and obstetric histories that were associated with normal fetal growth. Consenting women underwent serial (up to 5) sonographic evaluations of amniotic fluid between 15 and 40 weeks of gestation after being assigned randomly to 1 of 4 gestational age observation schedules. Twelve United States perinatal centers participated, and all sonograms were performed by credentialed sonographers who used identical, high-resolution equipment; caregivers were unaware of results but were notified for oligohydramnios. Women (n=597) who were subsequently found to have clinically significant antepartum complications were excluded. Racial/ethnic-specific nomograms for amniotic fluid index and single deepest pocket across gestation were developed with the use of linear mixed models with cubic splines; racial/ethnic differences were evaluated both with global and between-group tests. Median, 3rd, 5th, 10th, 90th, 95th and 97th percentile values were also estimated. We further considered the possible confounding effects of selected maternal characteristics and the estimated fetal weight at each sonogram. A total of 1719 pregnant women met inclusion criteria and had available data. These included 480 non-Hispanic white women, 418 non-Hispanic black women, 485 Hispanic women, and 336 Asian women. Both the amniotic fluid index and the single deepest pocket varied across gestation with maximal values at 26 and 33 weeks of gestation, respectively. Statistically significant differences were observed by maternal race/ethnicity. The between-group differences that were observed at 17-22 and 35-40 weeks of gestation remained statistically significant after adjustment for maternal characteristics and estimated fetal weight. These between-group racial/ethnic differences were most prominent after 35 weeks of gestation and at the extremes of dispersion (3rd and 97th percentiles). All 3rd and 97th percentile amniotic fluid index values were within the range of commonly used cutoffs to define oligohydramnios (≤5 cm) and polyhydramnios (≥25 cm). However, the 3rd percentile values ranged between 5.9 cm at 40 weeks of gestation and 10.1 cm at 25-27 weeks of gestation; the 97th percentile values ranged between 24.8 cm at 38 weeks of gestation and 15.7 cm at 15 weeks of gestation. Sonographic amniotic fluid volume estimates vary by racial/ethnic group, but the absolute differences appear to be small and may not be clinically significant. Selected maternal characteristics and estimated fetal weight did not affect the racial/ethnic differences. Between-group differences are maximal after 35 weeks of gestation and at the extremes of the upper and lower dispersion estimates. Given the observed variability in extreme (3rd and 97th percentile) dispersion values over the gestation, use of single cutoffs to define out-of-range measurements may not be appropriate clinically. These data might form a contemporary United States standard for amniotic fluid estimation that uses the amniotic fluid index and the single deepest pocket.

Paternal age and the risk of low birth weight and preterm delivery: a Finnish register-based study

BackgroundBased on existing studies, there is no conclusive evidence as to whether and why paternal age matters for birth outcomes.MethodsWe used Finnish population registers on 106 652 children born 1987–2000....

Effect of maternal age, height, BMI and ethnicity on birth weight: an Italian multicenter study.

To assess the effect of maternal age, height, early pregnancy body mass index (BMI) and ethnicity on birth weight. A cross-sectional study was conducted on more than 42,000 newborns. Ethnicity was defined by maternal country of birth or, when missing (<0.6% of records), by citizenship. The effect of maternal characteristics on birth weight was evaluated with general linear models. Maternal height and BMI, although not age, significantly affected birth weight. Among Italian babies, 4.7% of newborns were classified as appropriate-for-gestational age (AGA) (birth weight between the 10th and the 90th centile) according to the country-specific Italian Neonatal Study (INeS) charts and were re-classified as either large-(LGA) (birth weight >90th centile) or small-(SGA) (birth weight <10th centile) for gestational age (GA) after adjustment for maternal characteristics. On the contrary, 1.6% of Italian newborns were classified as SGA or LGA according to the INeS charts and re-classified as AGA after adjustment. Maternal ethnicity had a significant impact on birth weight. Specifically, babies born to Senegalese mothers were the lightest, whilst babies born to Chinese mothers were the heaviest. Maternal height and early pregnancy BMI, should be considered in the evaluation of birth weight. The effect of ethnicity suggests the appropriateness of ethnic-specific charts. Further studies are necessary to determine if changes in birth weight classification, may translate into improved detection of subjects at risk of adverse outcomes.

Parental population exposure to historical socioeconomic and political periods and grand-child’s birth weight in the Lifeways Cross-Generation Cohort Study in the Republic of Ireland

Exposure to deprived socioeconomic conditions during the peri-conception and early childhood periods can have a negative long-term impact on individuals’ health and that of their progeny. We aimed to examine whether relatives’ birth period affected index-child (grand-child) birthweight status in the Lifeways Cross-Generation Cohort in the Republic of Ireland. Participants were 943 mothers and offspring, 890 fathers, 938 maternal grandmothers (MGM), 700 maternal grandfathers (MGF) 537 paternal grandmothers (PGM) and 553 paternal grandfathers (PGF). Index-child’s birthweight was sex-for-gestational age standardised (UK1990 population), and then classified into low birthweight (≤10th percentile) and high-birthweight (≥90th percentile) and compared against normal-birthweight (>10th to <90th percentiles). Four adult birth periods were considered: The Free State (FS, 1916-1938); Emergency Act (EA, 1939-1946); Post-World War-II Baby-Boom (PWWII-BB, 1947-1964); and Modern Ireland (MI, 1964 onwards). Logistic regression was used to assess the crude and adjusted relationship between index-child’s birthweight status and relatives’ birth periods.Overall, there were 8.7% (n=82) index-children in the low-birthweight category, 77.9% (n=735) and 13.4% (n=126) within the normal and high birthweight groups respectively. Index-children whose mothers were born during the PWWII-BB had higher birthweight infants (Crude OR(COR)=1.81 (1.08–3.03) which remained the case only for male index-children when adjusted for co-variables (Adjusted OR(AOR)=4.61(1.71–12.42)). Parents’ combined PWWII-BB birth period was positively associated with male index-child higher birthweight, even adjusted for maternal characteristics (AOR=4.60(1.69–12.50)). MGFs born during the EA were more likely to have grandchildren with low birthweight after adjustment for maternal characteristics (AOR=2.45(1.03-5.85)), particularly for female index-children (AOR=4.74(1.16–19.25)). Both PGMs and PGFs born during the FS period had higher birthweight grandchildren, adjusted for maternal-related co-variables (PGM, AOR=3.23(1.21–8.63); PGF, AOR=3.93(1.11–13.96)), with the effect of PGM more evident in her granddaughter (AOR=6.53(1.25–34.04)). In conclusion, there is some evidence that period of grandparental birth is associated with their grandchildren’s birthweights, suggesting that transgenerational exposures may be particular to historical context, meriting further exploration.

Perinatal mortality associated with induction of labour versus expectant management in nulliparous women aged 35 years or over: An English national cohort study

BackgroundA recent randomised controlled trial (RCT) demonstrated that induction of labour at 39 weeks of gestational age has no short-term adverse effect on the mother or infant among nulliparous women aged ≥35 years. However, the trial was underpowered to address the effect of routine induction of labour on the risk of perinatal death. We aimed to determine the association between induction of labour at ≥39 weeks and the risk of perinatal mortality among nulliparous women aged ≥35 years.Methods and findingsWe used English Hospital Episode Statistics (HES) data collected between April 2009 and March 2014 to compare perinatal mortality between induction of labour at 39, 40, and 41 weeks of gestation and expectant management (continuation of pregnancy to either spontaneous labour, induction of labour, or caesarean section at a later gestation). Analysis was by multivariable Poisson regression with adjustment for maternal characteristics and pregnancy-related conditions. Among the cohort of 77,327 nulliparous women aged 35 to 50 years delivering a singleton infant, 33.1% had labour induced: these women tended to be older and more likely to have medical complications of pregnancy, and the infants were more likely to be small for gestational age.Induction of labour at 40 weeks (compared with expectant management) was associated with a lower risk of in-hospital perinatal death (0.08% versus 0.26%; adjusted risk ratio [adjRR] 0.33; 95% CI 0.13–0.80, P = 0.015) and meconium aspiration syndrome (0.44% versus 0.86%; adjRR 0.52; 95% CI 0.35–0.78, P = 0.002). Induction at 40 weeks was also associated with a slightly increased risk of instrumental vaginal delivery (adjRR 1.06; 95% CI 1.01–1.11, P = 0.020) and emergency caesarean section (adjRR 1.05; 95% CI 1.01–1.09, P = 0.019). The number needed to treat (NNT) analysis indicated that 562 (95% CI 366–1,210) inductions of labour at 40 weeks would be required to prevent 1 perinatal death. Limitations of the study include the reliance on observational data in which gestational age is recorded in weeks rather than days. There is also the potential for unmeasured confounders and under-recording of induction of labour or perinatal death in the dataset.ConclusionsBringing forward the routine offer of induction of labour from the current recommendation of 41–42 weeks to 40 weeks of gestation in nulliparous women aged ≥35 years may reduce overall rates of perinatal death.