#Preconception #vitamin D and #pregnancy outcomes: what’s the link?

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  • The Lancet Diabetology


Vitamin D deficiency during pregnancy is associated with adverse pregnancy outcomes, although the association between preconception vitamin D concentrations and livebirth is unknown. We aimed to assess the association between preconception vitamin D and pregnancy outcomes among women with proven fecundity.


We did a secondary analysis of a prospective cohort from the block-randomised, double-blind, placebo-controlled EAGeR trial. Women aged 18–40 years with one to two previous pregnancy losses were recruited from June 15, 2007, to July 15, 2011, at four clinical sites in the USA and followed up for up to six menstrual cycles while attempting pregnancy and throughout pregnancy if they conceived. Serum 25-hydroxyvitamin D was measured at baseline (preconception) and 8 weeks of gestation. Outcomes of interest included clinical pregnancy, time to pregnancy, pregnancy loss, and livebirths. Risk ratios (RRs) and 95% CIs for livebirths, pregnancy, and pregnancy loss were estimated with weighted log-binomial regression. To assess time to pregnancy, we used discrete time Cox proportional hazards models to calculate fecundability odds ratios (FORs) with 95% CIs. EAGeR is registered with, number NCT00467363.


1191 women had available data on preconception 25-hydroxyvitamin D concentrations. 555 (47%) women were classified as having sufficient concentrations (≥75 nmol/L) and 636 (53%) as having insufficient concentrations (<75 nmol/L). Women with sufficient preconception 25-hydroxyvitamin D were more likely to achieve clinical pregnancy (adjusted RR 1.10 [1.01–1.20]) and livebirth (1.15 [95% CI 1.02–1.29]) than were women with insufficient concentrations. Among women who achieved pregnancy, sufficient preconception 25-hydroxyvitamin D, but not that at 8 weeks of gestation, was associated with reduced risk of pregnancy loss (preconception RR per 25 nmol/L 0.88 [95% CI 0.77–0.99]; 8 weeks of gestation 0.98 [0.95–1.01]). No association was observed with fecundability in women with sufficient versus those with insufficient preconception 25-hydroxyvitamin D concentrations (adjusted FOR 1.13 [95% CI 0.95–1.34]).


Sufficient preconception 25-hydroxyvitamin D (≥75 nmol/L) was associated with increased likelihood of pregnancy and livebirth. Increased vitamin D concentrations before conception, but not in early pregnancy, were associated with reduced pregnancy loss.


National Institutes of Health and Doris Duke Charitable Foundation.

#Very obese women should lose weight during #pregnancy

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  • Noticias Médicas Univadis

Contrary to current recommendations, a new study suggests that very obese women should lose weight during pregnancy.

Researchers examined data on consecutive singleton term live births delivered at the maternity unit of the University South Reunion Island over a 16.5-year period from 2001 to 2017. They recorded pre-pregnancy body mass index (BMI), weight gain, and weight of the baby, for 52,092 women who gave birth at full term.

They found that only women with a normal BMI had a balanced risk of having a small or large for gestational age infant (both 10% risk); a crossing point they called the maternal foetal corpulence symbiosis (MFCS). They then examined how this MFCS shifted with BMI and weight gained during pregnancy and pinpointed the optimal weight gain/loss for each BMI category.

The researchers said that while widely used 2009 recommendations from the Institute of Medicine are adequate for normal and over-weighted women, a woman with a BMI of 17 should gain about 22kg instead of the recommended 12.5-18kg. An obese woman with a BMI of 32 should gain 3.6kg instead of the recommended 5-9kg, while women with a BMI of 40 should lose 6kg.

#Is #genital chlamydia infection in pregnancy associated with #risk for preterm birth?

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  • The Lancet Infectious Diseases

Background Chlamydia trachomatis is one of the most commonly diagnosed sexually transmitted infections worldwide, but reports in the medical literature of an association between genital chlamydia infection and adverse obstetric outcomes are inconsistent.

Methods The Western Australia Data Linkage Branch created a cohort of women of reproductive age by linking records of birth registrations with the electoral roll for women in Western Australia who were born from 1974 to 1995. The cohort was then linked to both chlamydia testing records and the state perinatal registry for data on preterm births and other adverse obstetric outcomes. We determined associations between chlamydia testing, test positivity, and adverse obstetric outcomes using multivariate logistic regression analyses.

Findings From 2001 to 2012, 101 558 women aged 15 to 38 years had a singleton birth. Of these women, 3921 (3.9%) had a spontaneous preterm birth, 9762 (9.6% of 101 371 women with available data) had a baby who was small for gestational age, and 682 (0.7%) had a stillbirth. During their pregnancy, 21 267 (20.9%) of these women had at least one chlamydia test record, and 1365 (6.4%) of those tested were positive. Before pregnancy, 19 157 (18.9%) of these women were tested for chlamydia, of whom 1595 (8.3%) tested positive for chlamydia. Among all women with a test record, after adjusting for age, ethnicity, maternal smoking, and history of other infections, we found no significant association between a positive test for chlamydia and spontaneous preterm birth (adjusted odds ratio 1.08 [95% CI 0.91–1.28]; p=0.37), a baby who was small for gestational age (0.95 [0.85–1.07]; p=0.39), or stillbirth (0.93 [0.61–1.42]; p=0.74).

Interpretation A genital chlamydia infection that is diagnosed and, presumably, treated either during or before pregnancy does not substantially increase a woman’s risk of having a spontaneous preterm birth, having a baby who is small for gestational age, or having a stillbirth.

Funding Australian National Health and Medical Research Council.

#ADHD Drugs Associated With Modest Risks During #Pregnancy

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Norra MacReady

Two large studies of pregnant women with attention-deficit hyperactivity disorder (ADHD) suggest that stimulant medications taken during pregnancy are associated with a modestly increased risk for perinatal and placental abnormalities. The authors of both studies, though, caution that those risks must be weighed against those of untreated ADHD.

If the medication is essential to manage a woman’s symptoms, “we do not find that our results concerning neonatal complications justify abstaining from therapy,” Ulrika Nörby, MSc Pharm, PhD, lead author of one of the studies, told Medscape Medical News. “Poorly controlled ADHD symptoms might result in poorer adherence to antenatal care, an unhealthier lifestyle and increased maternal stress that, in turn, can affect the fetus negatively.”

Jacqueline M. Cohen, PhD, lead author of the other study, echoed that point. “The increases in risk identified do not warrant abstaining from critical treatment,” she told Medscape Medical News. “It is important to balance the benefits of treatment, which may improve functioning, including maintaining family relationships, adherence to prenatal care, and avoidance of substance abuse.”

If anything, the results are reassuring because they suggest that “ADHD medications, taken in a controlled fashion, under the care of a doctor, with regular prenatal visits, have good pregnancy outcomes,” said Tina A. Nguyen, MD, assistant professor of maternal-fetal medicine in the Department of Obstetrics and Gynecology, University of California, Los Angeles Health/David Geffen School of Medicine. Dr. Nguyen was not involved in either study.

Effects on the Infant

In their study, published online today in Pediatrics, Dr. Nörby, from the Centre of Reproduction Epidemiology, Tornblad Institute, Department of Clinical Sciences, Lund University in Sweden, and colleagues analyzed singleton births recorded in the Swedish Medical Birth Register (MBR) between July 1, 2006, and December 31, 2014. The MBR captures essentially all births in Sweden and is linked to three other national registers that contain data on prescription drugs dispensed at Swedish pharmacies and infants admitted to neonatal intensive care units (NICUs).

The final cohort consisted of 964,734 infants, of whom 1591 (0.2%) were exposed to ADHD drugs during gestation, and another 9475 (1%) whose mothers used ADHD medications before or after, but not during, pregnancy. Stimulants accounted for 1464 (92%) of the in utero exposures, but 165 infants were born to women who used atomoxetine during pregnancy.

The rate of NICU admission among infants exposed to ADHD drugs during pregnancy was higher than that of infants whose mothers never used these agents (adjusted odds ratio [aOR], 1.5; 95% confidence interval [CI], 1.3 – 1.7), after adjustment for a variety of potential confounding factors, such as birth year, maternal age, body mass index, and smoking status, and maternal use of other drugs, such as opioids and antiepileptics. The risk also was increased in comparison with children whose mothers used the medication before or after pregnancy (aOR, 1.2; 95% CI, 1.1 – 1.4).

Maternal use of ADHD medication during pregnancy also was associated with a higher frequency of central nervous system disorders, such as seizures and congenital hypotonia, compared with no use (aOR, 1.9; 95% CI, 1.1 – 3.1) or use before or after pregnancy (aOR, 1.8; 95% CI, 1.0 – 3.3; P = .05). In addition, ADHD drug treatment  during pregnancy was also associated with an elevated risk for preterm delivery (aOR, 1.3; 95% CI, 1.1 – 1.6) compared with no use

Compared with the control group, women who used ADHD medications were significantly younger and were  more likely to be obese, to be nulliparous, to smoke, to use other medications, and to live without the child’s father. These differences were especially pronounced among women treated with ADHD drugs while pregnant.

These demographic differences suggest that women who need ADHD treatment during pregnancy “in many ways are a vulnerable group,” Dr Nörby told Medscape Medical News.

Consider the Context

In fact, these findings should be interpreted cautiously precisely because of the differences between the women in this study, said Sue Varma, MD, clinical assistant professor of psychiatry at the New York University Langone Medical Center in New York City. For that reason, “the results can’t at this point be generalized to a population at large,” she told Medscape Medical News.

Given the potential for risk to the fetus, “I would want to understand what is the mother’s baseline level of functioning, and ideally I would recommend a taper off the medication, if possible,” said Dr Varma, who was not involved in either study. However, she added, “if there has been a significant level of impairment, and medication is necessary, I would indeed consider it.”

Placental and Perinatal Effects

In the second study, published in the December issue of Obstetrics & Gynecology, Dr Cohen, a postdoctoral research fellow in the Department of Epidemiology, Harvard T.H. Chan School of Public Health in Boston, Massachusetts, and coauthors evaluated the effects of stimulant medication for ADHD on the risk for preeclampsia, placental abruption, fetal growth restriction, and preterm birth among women enrolled in Medicaid who gave birth between 2000 and 2010.

They compared outcomes from women taking amphetamine-dextroamphetamine or methylphenidate monotherapy with outcomes among women who did not receive a prescription for any ADHD stimulant medication during the 3 months before pregnancy through 140 days after their last menstrual cycle.

To control for the possibility that ADHD was itself a risk factor, they also compared the women taking stimulants to those using atomoxetine, which they described as “a nonstimulant ADHD medication used in cases in which other stimulants are ineffective or need to be avoided as a result of side effects or potential for abuse.”

The final cohort consisted of 1,466,792 women, including 4846 who used stimulants for ADHD at some time during pregnancy, 453 who used atomoxetine, and 1,461,493 in the control group.

After adjustment for demographic factors; multifetal gestation; use of alcohol, tobacco, and other drugs; obesity or overweight; and presence of certain health conditions, stimulant use was associated with a relative risk (RR) for preeclampsia of 1.29 (95% CI, 1.11 – 1.49) and amphetamine-dextroamphetamine use with an RR of 1.33 (95% CI, 1.12 – 1.58), compared with no exposure to these agents.

Similarly, stimulant use was associated with an adjusted RR for placental abruption of 1.13 (95% CI, 0.88 – 1.44), 0.91 for infants born small for gestational age (95% CI, 0.77 – 1.07), and 1.06 for preterm birth (95% CI, 0.97 – 1.16), compared with no exposure. Atomoxetine use was not associated with any of the outcomes studied in crude or adjusted analyses.

In a comparison of women who discontinued stimulant monotherapy after the first half of pregnancy, compared with those who continued it, continuation was associated with an adjusted RR for preterm birth of 1.30 (95% CI, 1.10 – 1.55). Continuation also was associated with an adjusted RR for preeclampsia of 1.26 (95% CI, 0.94 – 1.67), 1.08 for placental abruption (95% CI, 0.67 – 1.74), and 1.37 for being born small for gestational age (95% CI, 0.97 – 1.93).

Although stimulants were associated with an increased risk for preeclampsia and preterm birth, “the absolute increases in risks are small and thus, women with significant ADHD should not be counseled to suspend their ADHD treatment based on these findings,” the authors write.

Taken together, the studies “point to a potential increased risk of preterm birth associated with stimulant treatment,” Dr Cohen told Medscape Medical News.“Our study also suggests that stimulant ADHD medications modestly increase the risk of preeclampsia. But we found no evidence of increased risk of placental complications associated with atomoxetine, which suggests that nonstimulant ADHD medications may be safer to use in pregnancy, though more research is needed due to the smaller number exposed.”

“These studies provide some reassurance to pregnant women who strongly benefit from treatment with ADHD medication that the potential increases in risk for perinatal complications are modest,” she concluded.

Dr Cohen has received salary support from a research grant from GlaxoSmithKline for unrelated work. Other coauthors report receiving salary or research funding or institutional training grants from GlaxoSmithKline, Eli Lilly, Pfizer, UCB, Teva, Boehringer-Ingelheim, Takeda, Bayer, Asisa, Pacira, Baxalta, Optum, and Merck. None of the other researchers or commentators have disclosed relevant financial relationships.

Pediatrics. Published online November 1, 2017. Abstract

Obstet Gynecol. 2017;130:1192-1201. Abstract

Autism risk linked to fever during pregnancy

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Prenatal exposure to maternal fever during the second trimester raised odds of autism spectrum disorder by 40 per cent.

Fever during pregnancy may raise the risk for autism spectrum disorder (ASD), according to a new study published in Molecular Psychiatry. ASD risk was increased by 34 per cent when mothers reported fever at any time during pregnancy, and by 40 per cent in the second trimester. Risk of ASD was increased by over 300 per cent among children of women who reported three or more fevers after the 12th week of pregnancy.

Risks were minimally mitigated when women used acetaminophen for fever in the second trimester. Although there were no cases of ASD when mothers used ibuprofen, the sample was too small to draw conclusions.

Analysis did not indicate an association between risk and maternally-reported symptoms of infection in individual organ systems. An ongoing study is testing blood samples collected at mid-pregnancy and at birth to explore the possible role of specific infectious agents.

“Our results suggest a role for gestational maternal infection and innate immune responses to infection in the onset of at least some cases of autism spectrum disorder,” said first author Mady Hornig, associate professor of epidemiology and director of translational research at Columbia University.

Can Vitamin D in pregnancy prevent childhood asthma?

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For the first time, research has shown that higher prenatal vitamin D levels can effectively alter the immune response of infants.

Vitamin D is a well-recognised immune modulator, and vitamin D deficiency during pregnancy is hypothesised to influence disease development in offspring.

A new study has demonstrated for the first time that prenatal vitamin D supplements can positively modify the immune system of neonates, which could help to protect against asthma and respiratory infections.

As part of the study, women were randomised to receive either a supplement of 4,400IU of vitamin D3 per day during the second and third trimesters of pregnancy versus the recommended daily intake (RDI) of 400IU/day.
Supplementation with 4400IU resulted in an enhanced broad-spectrum proinflammatory cytokine response of cord blood mononuclear cells to innate and mitogenic stimuli, with an average 1.7- to 2.1-fold increase in levels of several proinflammatory cytokines (GM-CSF, IFN-γ, IL-1β, IL-6, and IL-8), a higher gene expression level of TLR2 and TLR9, a greater than 4-fold increase in IL-17A production after polyclonal T-cell stimulation, and an enhanced IL-10 response of cord blood mononuclear cells to dexamethasone treatment in culture.

The findings are published in the Journal of Allergy and Clinical Immunology .

Avoid these antibiotics in early pregnancy

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New research has identified an increased risk of miscarriage with these five common classes of antibiotics.

A Canadian study has identified an increased risk of miscarriage with the use of five common classes of antibiotics in early pregnancy.

The research, published in the Canadian Medical Association Journal (CMAJ), found the use of macrolides (excluding erythromycin), quinolones, tetracyclines, sulfonamides and metronidazole during early pregnancy was associated with an increased risk of spontaneous abortion. Nitrofurantoin exposure was not associated with an increased risk of miscarriage, which supports its use as an alternative to trimethoprim-sulfamethoxazole for the treatment of urinary tract infections during pregnancy.

Azithromycin and metronidazole were associated with a 65 per cent and 70 per cent increased risk of miscarriage respectively, while sulphonamides, tetracyclines, quinolones and clarithromycin more than doubled the risk. Results were similar regardless of whether penicillins or cephalosporins were used as comparators.

“Although antibiotic use to treat infections has been linked to a decreased risk of prematurity and low birth weight in other studies, our investigation shows that certain types of antibiotics are increasing the risk of spontaneous abortion, with a 60 per cent to two-fold increased risk,” explained senior author, Dr. Anick Bérard. “Nevertheless, the increased risk was not seen for all antibiotics, which is reassuring for users, prescribers, and policy-makers,” she added.