VANCOUVER, B.C. – The risk of congenital anomalies for a given pregnancy varies according to the time elapsed since the last pregnancy, a retrospective population-based cohort study of more than 46,000 women has shown.

Study results, reported at the annual meeting of the Society of Obstetricians and Gynaecologists of Canada, showed that the rate of congenital anomalies was lowest when the interpregnancy interval was 12-17 months and increased with both shorter and longer intervals. The pattern was similar for folate-dependent and folate-independent anomalies individually.

"A J-shaped relationship exists between interpregnancy interval and congenital anomalies," said principal investigator Dr. Innie Chen, a resident in the department of obstetrics and gynecology at the University of Alberta, Edmonton. "The observation that long intervals were associated with congenital anomalies as well as the preservation of the association for folate-independent anomalies suggests that the mechanism of the observed effect is unlikely to be mediated by folate deficiency alone.

"To date and to our knowledge, this is the most comprehensive data available on this topic. The implications of this study are broad and touch on prenatal risk assessment, prenatal counseling, and future recommendations regarding birth spacing and nutritional supplementation," she said.

But she also cautioned that it could be problematic to apply the findings to individual women who ask when is the best time to conceive again to minimize risk.

"This is an epidemiological study. Decisions for individuals depend on a lot of things, such as where they are in their life and their career situation," she explained. "But I think this data adds to the growing literature about the effect of interpregnancy interval and adverse perinatal outcomes, which we see again and again. Compared to 50 or 100 years ago, we have much better contraception, so I think it is within our control."

A variety of adverse perinatal outcomes – preterm birth, small for gestational age, low birth weight, and perinatal death – have shown a J-shaped association with interpregnancy interval.

"The most-often-cited postulated mechanism for the observed effect is a folate deficiency hypothesis, which is based on the observation that maternal serum levels are very low in the postpartum period," Dr. Chen said.

A previous retrospective cohort study found an association between both short and long interpregnancy intervals and major congenital malformations (Contraception 2009;80:512-8). But that study did not evaluate specific types of anomalies.

Dr. Chen and her colleagues began with data from the Alberta Perinatal Health Program Database, which collects information on all hospital and midwife births, and all terminations after 20 weeks’ gestation in the Northern part of the province.

They identified women who had a singleton delivery between 1999 and 2007 (the post–folate food fortification era, so that results would be applicable today) and who did not have a miscarriage between their first and second births (so that the interpregnancy interval was more reliable).

They then linked that data with data from other provincial databases to obtain more comprehensive maternal information and ascertain anomalies.

The working data set consisted of 46,559 pregnant women. The interpregnancy interval was 6-59 weeks’ gestation for 90% of them.

Most of the women were 20- to 34-years-old (83%) and para 2 (88%) at the time of the second delivery, and most of their infants had a gestational age of at least 37 weeks (93%) and a birth weight of at least 2,500 g (96%).

The rate of congenital anomalies did not vary significantly according to maternal age, maternal weight, smoking in pregnancy, or socioeconomic status, Dr. Chen reported.

For interpregnancy intervals of 59 months or less, there was a J-shaped association between the interval and the rate of congenital anomalies. The rate was lowest, at 1.9%, when the interval was 12-17 months.

It rose to a high of 2.5% when the interval was 0-5 months and 2.4% when the interval was 24-59 months. The corresponding odds ratios were 1.35 and 1.28, respectively.

The pattern was similar for folate-dependent anomalies (neural tube defects, cleft lip and palate, cardiovascular defects, urinary tract anomalies, and limb defects) and for folate-independent anomalies individually.

In addition, an interval of 0-5 months was associated with increased odds of specific anomalies, such as neural tube defects and heart defects, but not significantly so.

"We believe these results to be valid as they are consistent with and corroborate existing studies in the literature," said Dr. Chen.

"Future directions for research include changing the databases to capture more information on all terminations and folate supplementation, combining the databases for more statistical power, and checking other postulated mechanisms for the observed effect," she said.

Dr. Chen reported that she had no relevant financial disclosures.

Interpregnancy Interval Linked to Rate of Congenital Anomalies